Amoxycillin levels in human serum, bile, gallbladder, lung, and liver tissue

Amoxycillin levels were measured in the serum, bile, lung, gallbladder, and liver tissue in 19 cases of lung and 22 cases of cholecyst operations following intramuscular administration of 1 g amoxycillin. After 60-160 min, 4.4-5.6 mcg/g intact lung tissue and 1.5-3.9 mcg/g tumorous lung tissue concentrations were found, representing 41-48% and 15-32%, respectively, of the corresponding serum levels. Between 70 and 160 min when the ducts cysticus was open, the cystic bile contained 5.2-8.8 mcg/ml, the bile taken from the biliary ducts showed 10.9-13.2 mcg/ml, whereas the wall of the gallbladder and the liver tissue displayed 4.4-5.1 and 1.7-2.8 mcg/g amoxycillin levels. These levels represented 50-92, 118-136, 50-52 and 17-28% of the actual serum levels. As in the serum levels, the bile and tissue levels were about twice as high as those following ampicillin administration. The amoxycillin levels measured in the serum, bile, and other tissue tissues in most cases exceeded the minimal inhibitory concentrations for most of the bacteria usually considered. Therefore, amoxycillin can be applied successfully to treat respiratory and biliary infections.     

Treatment of experimental endocarditis due to Enterococcus faecalis using once-daily dosing regimen of gentamicin plus simulated profiles of ampicillin in human serum

We compared the efficacy of ampicillin, both alone and in combination with gentamicin given once a day (q.d.) or three times a day (t.i.d.), in the treatment of experimental enterococcal endocarditis. Ampicillin was administered by using humanlike pharmacokinetics that simulated the profiles of this drug in human serum. An open one-compartment mathematical model developed in this study was used to estimate the decreasing doses administered with a computer-controlled infusion pump that simulated in rabbits the human serum pharmacokinetics after intravenous administration of 2 g of ampicillin every 4 h. Animals with catheter-induced endocarditis were infected intravenously with 10(8) CFU of Enterococcus faecalis J4 (MICs and MBCs of ampicillin and gentamicin, 2 and 128 and 16 and 64 micrograms/ml, respectively) and were treated for 3 days with ampicillin alone or in combination with gentamicin at 2 mg/kg of body weight subcutaneously t.i.d. or at 6 mg/kg subcutaneously q.d. The serum ampicillin levels and pharmacokinetic parameters of the humanlike pharmacokinetics of ampicillin in rabbits were similar to those found in humans treated with 2 g of ampicillin intravenously. The results of therapy for experimental endocarditis caused by E. faecalis J4 showed that the residual bacterial concentration in aortic valve vegetation was significantly lower in the animals treated with combinations of ampicillin plus gentamicin given q.d. or t.i.d. than in those treated with ampicillin alone (P < 0.01). The dosing interval of gentamicin did not significantly affect (q.d. versus t.i.d.; P = 0.673) the therapeutic efficacy of the combination of ampicillin plus gentamicin.     

Antibiotic concentrations in ascitic fluid of patients with ascites and bacterial peritonitis

Thirty-six paired specimens of serum and ascitic fluid from 21 patients with peritonitis and ascites, most with sponetaneous bacterial peritonitis and alcoholic cirrhosis, were assayed for antibiotic content. Antibiotics assayed and number of determinations were gentamicin, 14; tobramycin, 7; ampicillin, 5; clindamycin, 3; penicillin G, 2; cephalothin, 2; chloramphenico, 2; and cefazolin, 1. In 31 pared specimens the ascitic fluid antibiotic concentration was about one half or more of the simultaneous serum level and in 17 assays exceeded 90% of the serum level. All antibiotics studied penetrated ascitic fluid equally well. Clinical response to antibiotic therapy was good in 12 of 16 patients with culture-proven bacterial peritonitis. Antibiotic levels in ascitic fluid exceeded the minimal inhibitory concentration of the infecting organisms in all but one patient who responded. Direct intraperitoneal instillation of antibiotics does not appear to be necessary routinely; however, there may be an initial lag of several hours before antibiotic concentrations is ascites achieve therapeutic levels.     

Rare pulmonary mycoses in patients with hematologic diseases

The fixed combination of ampicillin (2 g)/sulbactam (1 g) was administered as perioperative prophylaxis at induction of anesthesia in 20 patients undergoing spinal microneurosurgery. It was noteworthy that after the short infusion ampicillin and sulbactam penetrated rapidly from blood into the different tissues affected by the surgical procedures. The following mean concentrations were measured in tissues: muscle 32.3+/-6.5 mg/kg ampicillin and 18.6+/-2.9 mg/kg sulbactam (11.1 min), ligament 39.5+/-11.1 mg/kg ampicillin and 25+/-6.5 mg/kg sulbactam (13.8 min), bone 12+/-3.6 mg/kg ampicillin and 7+/-0.8 mg/kg sulbactam (20.6 min), disk 10.2+/-3.3 mg/kg ampicillin and 7.3+/-1.8 mg/kg sulbactam (44.2 min). The mean time of sampling is given in brackets. For a period of at least 2 h the levels of both drugs measured in serum and in the different tissues were above the MICs for bacteria involved in postoperative wound infections. The administration of ampicillin/sulbactam apparently achieved sufficiently, high antibiotic concentrations, even in bradytrophic tissues such as ligament, bone, and disk, and seemed to meet the pharmacological criteria for perioperative prophylaxis in spinal microneurosurgery.     

Comparison of concentrations of sulbactam-ampicillin administered by bolus injections or bolus plus continuous infusion in tissues of patients undergoing colorectal surgery

The concentrations of sulbactam and ampicillin were determined in sera and different abdominal tissues of 16 patients who underwent elective colorectal surgery. Patients were randomly allocated to two groups. At the time of induction of anesthesia, patients in group 1 (eight patients) were given 1,000 mg of sulbactam with 2,000 mg of ampicillin by intravenous bolus injection (3 min). This dose was administered again after 2 h by bolus injection by the same route. Patients in group 2 (eight patients) were given the same initial dose of sulbactam-ampicillin by bolus injection (3 min). Then, a continuous infusion of 1,000 mg of sulbactam with 2,000 mg of ampicillin in normal saline was immediately started and was administered over a 4-h period. Blood samples were collected to determine peak (10 min) and trough (end of surgery) antibiotic levels. Serial blood samples were also collected at predetermined periods (at the time of opening and closing of the abdominal cavity and at the time of surgical anastomosis). Abdominal wall fat, epiploic fat, and colonic wall tissue samples were collected simultaneously. Antibiotic concentrations were determined by high-performance liquid chromatography. Similar levels of the drugs in serum were observed for the two regimens of administration, with trough sulbactam levels of 33 +/- 16 and 37 +/- 22 microg/ml in groups 1 and 2, respectively, and trough ampicillin levels of 72 +/- 55 and 79 +/- 47 microg/ml in groups 1 and 2, respectively. Similar sulbactam concentrations were observed in abdominal tissues whichever regimen of administration was used; in fatty tissues the sulbactam concentrations ranged from 2.7 to 3.8 microg/g for group 1 and from 1.7 to 4.0 microg/g for group 2, and sulbactam concentrations in the colonic wall were 5.6 +/- 7.7 and 6.8 +/- 3.2 microg/g in groups 1 and 2, respectively (not significant). Again, no influence of the regimen of administration was observed on tissue ampicillin concentrations; in fatty tissues ampicillin concentrations ranged from 4.1 to 5.4 microg/g for group 1 and from 3.2 to 5.8 microg/g for group 2, and sulbactam concentrations in the colonic wall were 7.0 +/- 2.8 and 11.0 +/- 4.7 microg/g for groups 1 and 2, respectively (not significant). In most patients, the concentrations of ampicillin-sulbactam were greater than the MIC at which 50% of isolates are inhibited (MIC50) for Bacteroides fragilis in the fatty tissues. In the colonic wall, for most patients the concentrations of ampicillin-sulbactam were greater than the MIC90 for B. fragilis. No influence of the regimen of administration was observed on the ratio of the two components in the tissues investigated and in sera. In conclusion, a second intraoperative bolus injection or a continuous infusion were equally effective in maintaining sulbactam-ampicillin concentrations in abdominal tissues. The first method of administration can be recommended since it is easier to handle.     

Studies on the pattern of circulating steroids in the normal menstrual cycle. 2. Levels of 20alpha-dihydroprogesterone, 17-hydroxy-progesterone and 17-hydroxypregnenolone and the assessment of their value for ovulation prediction

Plasma levels of 20alpha-dihydroprogesterone, 17-hydroxyprogesterone and 17-hydroxypregnenolone were assayed daily in 15 normally menstruating women during a complete menstrual cycle. In order to ascertain the normalcy of the cycles studied, LH, progesterone and oestradiol were also determined daily. The pattern of 20alpha-dihydroprogesterone was very similar to that of progesterone. The levels found during the proliferative phase (around 240 pg/ml) increased significantly on the day of the LH-surge and reached values of approximately 3.7 ng/ml at the peak period of luteal activity. The plasma levels of 17-hydroxyprogesterone in the proliferative phase were around 380 pg/ml. The first significant increase occurred one day before the LH-surge and was followed by a sharp peak (approximately 1.5 ng/ml) which coincided with the LH peak. A significant decrease occurred after this peak, which reached a nadir two days after the LH-surge. This was followed by a second rise with a rather broad peak (about 1.8 ng/ml) around the 5th to 7th days after the LH-surge. The levels of 17-hydroxypregnenolone did not show any cyclic variation: from all figures a geometric mean value of 1.62 ng/ml was calulated with tolerance limits at 0.241 and 10.8 ng/ml. Individual day-to-day changes in steroid levels were assessed with regard to their potential for the early identification of the day of the LH-surge. A 17-hydroxyprogesterone value of 1.0 ng/ml, or more, was seen for the first time in the cycle on the day of the LH peak in 13 cycles and a progesterone + 17-hydroxyprogesterone level of at least 1.8 ng/ml in 14 of the 15 cycles studies. These data seem to warrant a study of the predictive value of progesterone and 17-hydroxyprogesterone assays in a much larger population.     

Caudal morphine in paediatric patients: a comparison of two different doses in children after major urogenital surgery

As we had an opportunity to take blood samples from a totally thyroidectomized patient who had attempted suicide by taking 2,000 microg of Levothyroxine (L-T4), the serum levels of thyroid hormones were sequentially measured to investigate the metabolism of circulating thyroid hormones in an athyreotic human. The serum concentrations of most thyroid hormones reached a peak on the second day, but the serum T3 level showed a peak one day later. The maximum concentrations of T4 (315 microg/l), FT4 (48.8 ng/l) and rT3 (0.80 microg/l) were very high, while the peak T3 level (1.92 microg/l) did not exceed the upper limit of the normal range. The serum T4 and rT3 levels returned to their normal range 13-17 days after the suicide attempt. The TSH level was suppressed rapidly and reached its nadir (0.044 mU/l) on the 6th day. During this period, the T1/2 and MCR of serum T4 were 10.4 days and 0.64 l/day, respectively, which values were almost equivalent to those observed during 15 days after discontinuation of the maintenance L-T4 therapy. In summary, the oral intake of a large amount of L-T4 at one time does not induce a proportional increase in the T3 level in an athyreotic person. The MCR of serum T4 is decreased and the T1/2 of serum T4 is prolonged, probably due to the lack of intrathyroidal deiodination. These findings support the conclusion that the D1 activity in the thyroid is one of the major determinants in the metabolic clearance of serum T4.     

The effect of maternally administered drugs on bilirubin concentrations in the newborn infant

The effects of drugs administered to pregnant women on bilirubin concentrations in 1,107 consecutively born infants are presented. Administration of narcotic agents, barbiturates, aspirin, chloral hydrate, reserpine, and phenytoin sodium all resulted in lowering of infant serum bilirubin concentrations. Diazepam and, to a lesser extent, oxytocin caused an elevation of infant serum bilirubin concentrations. Although many drugs were shown to alter serum bilirubin levels significantly, the clinical importance of such alterations was not dramatic except possibly in special circumstances. The phenothiazine derivatives, general or local anesthesia, sulfadimidine, ampicillin, and penicillin had no such effect on the newborn infant when given to the mother before delivery.     

Response of the primate secretory endometrium to subchronic hypercortisolemia

OBJECTIVE: To assess the impact of subchronic and moderate hypercortisolism on the secretory endometrium of the cynomolgus monkey. METHODS: Osmotic pumps containing hydrocortisone phosphate (HP) were implanted subcutaneously in each monkey on the first day of the menstrual cycle; each monkey also received pumps containing saline in another cycle. Blood was obtained three times per week and urine was collected daily for hormone analyses. Endometriectomy was performed 13 +/- 1 days after the serum estradiol (E2) peak in each study cycle. RESULTS: Infusion of HP elevated serum cortisol levels by an average of 70%. Mean serum progesterone (P) levels were decreased by 50% during the secretory phase of HP-treatment cycles by comparison with self-control cycles (P < .01); as a result, the mean endometrial glycogen concentration was reduced by 30% (P < .05) and the activity of 17 beta-hydroxysteroid dehydrogenase was decreased by 70% (P < .05). Serum E2 levels were not consistently elevated by HP treatment, but cytosolic estrogen receptor levels of the endometrium were decreased by 50% (P < .01), indicating increased estrogenic stimulation. Histologic development of the secretory endometrium was retarded, but the length of the secretory phase was not affected by the treatment. CONCLUSION: A moderate elevation of serum cortisol levels over one menstrual cycle consistently produced a reduction in serum P and a hypoprogestogenic-hyperestrogenic response of the secretory endometrium in the cynomolgus monkey.     

Relationship between symptom severity and steroid variation in women with premenstrual syndrome: study on serum pregnenolone, pregnenolone sulfate, 5 alpha-pregnane-3,20-dione and 3 alpha-hydroxy-5 alpha-pregnan-20-one

The relationship between symptoms of premenstrual syndrome (PMS) and serum levels of pregnenolone (Pe), pregnenolone sulfate (PS), 5 alpha-pregnane-3,20-dione (5 alpha-DHP), 3 alpha-hydroxy-5 alpha- pregnan-20-one (5 alpha-THP), LH, 17 beta-estradiol (E2), and progesterone (P) was investigated during 2 consecutive menstrual cycles in 12 patients using daily measurements. Corresponding hormones were also measured during 1 cycle in 8 control women. Pe, PS, 5 alpha-DHP, and 5 alpha-THP showed a significant cyclicity within menstrual cycles and a high rate of correlation with P variation in both PMS patients and controls. No significant difference was found between PMS patients and controls in average serum concentrations of Pe, PS, 5 alpha-DHP, 5 alpha-THP, and LH during the luteal phase, whereas a significantly higher level of E2 and a lower level of P were observed in PMS patients. The variation in symptom scores was compared with that in hormone levels within each woman. The symptom peak showed a delay of 3-4 days after the serum P, Pe, 5 alpha-DHP, and 5 alpha-THP peaks. However, the plasma PS peak appeared on the same day or only 1 day before the symptom peak in PMS patients. When comparing the 2 cycles studied, more negative symptoms occurred in cycles with higher luteal phase E2, Pe, and PS concentrations, whereas higher luteal phase 5 alpha-DHP and 5 alpha-THP concentrations were associated with improved symptom ratings in PMS patients. These results suggest that the mentioned steroids are related to the severity of distressing symptoms in PMS patients.     

Serum levels of cardiac troponin I and troponin T in estimating myocardial infarct size soon after reperfusion

BACKGROUND: Cardiac troponin I (TnI) and troponin T (TnT) are highly specific myocardial markers. OBJECTIVE: To determine whether their serum levels can be used to estimate myocardial infarct size soon after reperfusion. METHODS: We measured the serum levels of TnI, TnT, and creatine kinase every 3 h, and the serum cardiac myosin light chain I (MLCI) every 24 h, in 42 patients with acute myocardial infarction in whom reperfusion therapy had successfully been performed. We calculated the severity of regional hypokinesis by analyzing the follow-up ventriculograms with the centerline method. RESULTS: The time from reperfusion to the peak level for TnI was 6.1 +/- 3.5 h, significantly shorter than those for creatine kinase (7.5 +/- 4.1 h) and MLCI (55 +/- 28 h). The time to peak level for TnT (6.8 +/- 4.0 h) differed significantly from that for MLCI but not from that for creatine kinase. There was a significant correlation between the peak levels of TnI and TnT (r = 0.86). The peak TnI and TnT levels were correlated well to the peak creatine kinase level (r = 0.67 and 0.69, respectively), total creatine kinase release (r = 0.66 and 0.66), and the peak MLCI level (r = 0.71 and 0.80). We observed excellent correlations between the peak levels of TnI and TnT, and regional hypokinesis (r = -0.84 and -0.85, respectively). These were comparable to the correlations between regional hypokinesis and the peak creatine kinase level (r = 0.75), total creatine kinase release (r = -0.72), and the peak MLCI level (r = -0.76). CONCLUSIONS: These results suggest that the peak serum levels of TnI and TnT in patients with successful reperfusion are accurate and early indices of infarct size.     

Serum insulin-like growth factor-I, insulin-like growth factor binding protein-3, sex steroids, osteocalcin and bone mineral density in male and female rats

Although it has been reported that the rate of weight gain and linear growth increases markedly during puberty in rats, little is known about the relationship between endocrine changes and bone mineral density (BMD) changes upon sexual maturation in these animals. The aim of this study was to examine the levels of serum insulin-like growth factor-I (IGF-I), IGF binding protein (IGFBP)-3, sex steroids and osteocalcin, and the changes in BMD in normal aging male and female rats. Male rats exhibited increases in serum IGF-I and IGFBP-3 concentrations before increases in serum testosterone levels. IGF-I and testosterone peaked at 9 weeks of age, and thereafter remained in a steady state, whereas IGFBP-3 reached a peak at 7 weeks of age, and then gradually declined. A strong correlation between serum IGF-I and IGFBP-3 levels was found in subjects 3-9 weeks old. A highly significant correlation between serum IGF-I and testosterone levels was also found. In females, serum 17 beta-estradiol, IGF-I and IGFBP-3 levels increased gradually from 3 to 5 weeks old, peaked at 9 weeks, and then decreased slowly thereafter. The correlation coefficient between serum IGF-I and IGFBP-3 was highly significant. The correlation coefficient between serum IGF-I and 17 beta-estradiol levels was weak, although it was strongest when the subjects were 3-9 weeks old. Serum osteocalcin is a marker of bone formation; its level remained relatively high from 3 to 9 and from 3 to 7 weeks of age in males and females, respectively, although osteocalcin in both sexes declined gradually with age. As for bone mass, sharp increases in BMD in the tibia, femur and lumbar vertebrae appeared earlier in female than in male rats, and the BMD in females tended to be higher than in males between 5 and 9 weeks old. After 9 weeks of age, BMD in males was higher than that in females, as BMD in males continued to increase whereas females tended to remain in a steady state after this stage. The correlation coefficients between tibial BMD and serum IGF-I or IGFBP-3 levels were highly significant when the subjects were from 3 to 9 weeks old. Taken together, these results suggest that BMD development occurs earlier in female than in male rats. This sex-related difference in changes in the BMD pattern may result from the earlier onset of puberty in females, and from sex-specific differences in concentrations of IGF-I, IGFBP-3 and sex steroids during maturation.     

Successful treatment with ampicillin and fluoroquinolones of human endocarditis due to high-level gentamicin-resistant enterococci

Two cases of endocarditis, one caused by high-level gentamicin-resistant Enterococcus durans and the other by high-level gentamicin- and glycopeptide-resistant Enterococcus faecalis. successfully treated with a combination of ampicillin and a fluoroquinolone are reported. Both strains were susceptible to ampicillin. Enterococcus faecalis was susceptible to ciprofloxacin and to ofloxacin, but Enterococcus durans was moderately resistant to these agents. Microbiological and clinical cure was obtained with a 6-week course of ampicillin plus ciprofloxacin in one case and with ofloxacin in the second case due to intolerance to ciprofloxacin. The efficacy of the treatment was predicted in vitro by time-kill studies and by adequate serum bactericidal titres.     

Gentamicin dosage in children with extensive burns

During the treatment of Gram-negative bacillary infections in severely burned children, it was noted that administration of standard dosages of gentamicin commonly produced inadequately low serum concentrations of the antibiotic. Pharmakokinetic studies demonstrated that mean peak serum gentamicin levels were significantly lower in 18 burned children as compared with peak serum levels in five unburned children. Furthermore, inadequately low peak serum levels (less than 3.0 mug/ml) were observed in 15 of 18 burned children and in only one unburned child. Clearance studies in two children suggested that the increased requirement for gentamicin can result from either loss of the antibiotic across burn wounds or increased urinary excretion. These studies indicate that the therapy of severe infections in children with major burns often requires administration of gentamicin at higher doses and more frequent intervals than usually employed.     

Effects of isometric exercise on serum creatine phosphokinase activity

The effect of isometric exercise on serum creatinine phosphokinase (CPK) activity in 14 psychotic patients in remission and ten normal controls was studied. The increases in serum CPK activity at 18 and 42 hours after exercise were no significantly different in patients and controls. The postexercise serum CPK activities in the patients were significantly less than the peak serum CPK levels when they were psychotic. There were no significant correlations between postexercise serum CPK activity and preexercise or peak serum CPK activity in the patient group. It is unlikely that increased isometric muscle tension is a major causative factor in the increased serum CPK levels frequently found in psychotic patients.     

Familial insensitivity of the pituitary and periphery to thyroid hormone: a case report in two generations and a review of the literature

A clinically euthyroid 2-yr-old girl was found to have diffuse goiter that measured 3 X 5.5 cm with a prominent systolic bruit. Serum free T4 (3.4 ng/dl) and serum T3 (360 ng/dl) remained elevated for the next 10 months even though she remained clinically euthyroid. Elevation of serum free T4 (3.0 ng/dl) and serum T3 (265 ng/dl) was also present in the 24-yr-old nongoitrous mother who had symptoms and signs of hypothyroidism. Following intravenous injection of TRH, basal TSH levels of 2.7 and 2.8 microunits/ml increased to peak values of 17 and 21 microunits/ml at 30 min in the daughter and mother, respectively. Administration of exogenous T3 followed by sequential testing with boluses of TRH revealed retention of TSH responsiveness in both daughter and mother during pretreatment with dosage regimens of T3 below 125 micrograms daily. Maintenance of TSH responsiveness to TRH in the presence of elevated levels of serum free T4 and serum T3 indicates relative pituitary insensitivity to thyroid hormone which could be overridden by increasing the circulating levels of serum T3 three to fivefold over the already elevated basal levels. The absence of clinical signs of thyrotoxicosis indicates peripheral insensitivity to thyroid hormone with elevated circulating concentrations presumptively compensating for the defect. Resistance to thyroid hormone in two generations of the same family suggests genetic inheritance, and is concordant with four earlier reports of familial aggregation in this syndrome.     

Inhibition of omeprazole induced hypergastrinaemia by SMS 201-995, a long acting somatostatin analogue in man

Whether the long acting somatostatin analogue SMS 201-995 (octreotide, Sandostatin) could inhibit the basal and meal stimulated hypergastrinaemia and hyperpepsinogenaemia induced by omeprazole was investigated. Eight healthy subjects were randomised to receive five day courses of SMS 201-995 (25 micrograms subcutaneously three times daily), omeprazole (40 mg once a day), a combination of both drugs, or placebo. Basal and meal stimulated serum gastrin and basal serum pepsinogen A and C values were measured the day before treatment, on day five of treatment, and the day after each course of treatment. Omeprazole caused significant increases in basal and meal stimulated peak and integrated serum gastrin values and pepsinogen A and C levels, which were still significantly raised the day after stopping omeprazole treatment. Giving SMS 201-995 with omeprazole significantly reduced any omeprazole induced increases in basal and meal stimulated peak and integrated serum gastrin levels; serum pepsinogen A and C values were significantly inhibited too. Serum gastrin values during combined therapy were not significantly different from those during placebo treatment, whereas pepsinogen A and C levels were still significantly raised. On the day after stopping combined therapy, basal and meal stimulated peak and integrated serum gastrin and serum pepsinogen C (but not pepsinogen A) levels were not significantly different from values obtained on the day after stopping omeprazole alone. SMS 201-995 without omeprazole significantly inhibited basal and meal stimulated peak and integrated serum gastrin levels. Pepsinogen A was also significantly inhibited by SMS 210-995, but the reduction in pepsinogen C failed to reach statistical significance. In conclusion, SMS 201-995 prevents basal and meal stimulated increases in serum gastrin during omeprazole therapy. This finding may have clinical importance in the few patients who have pronounced hypergastrinaemia because of profound long acting acid inhibition.     

Gas chromatographic and gas chromatographic-mass spectrometric analysis of ampicillin

A method was developed for the quantitative gas chromatographic (GC) determination of ampicillin. The procedure requires silylation iwth hexamethyldisilazane, trimethylchlorosilane, trimethylsilylimidazole and N,O-bis(trimethylsilyl)acetamide in pyridine and subsequent GC on an OV-17 column, using 5 alpha-cholestane as an internal standard. The method was applied to the determination of ampicillin in some pharmaceutical products. The characteristics of the mass spectra and the derivatization GC of ampicillin are also discussed.     

Prediction of gentamicin serum levels using a one-compartment open linear pharmacokinetic model

The accuracy of predicting serum gentamicin levels based on a one-compartment open linear pharmacokinetic model was studied. Twenty-two patients accounted for 59 serum gentamicin levels which were measured by microbiologic assay and compared with predicted serum levels determined by pharmacokinetic calculation. Seventeen serum levels were collected at peak times, 15 at trough time and 27 at times between peak and trough. Forty-nine of the levels were obtained from patients with impaired renal function. Predicated gentamicin levels correlated well with measured serum levels (r = 0.85, p less than 0.001). Of the measured levels, 56% were within +/- 1 microgram/ml of the predicted levels. Of 49 levels collected from patients with impaired renal function, 59% were within +/- 1 microgram/ml of the predicted level. In 13 patients from whom multiple serum gentamicin levels were collected and predictions based on half-life or elimination rate obtained by fitting the first level, 83% of the measured levels were within +/- 1 microgram/ml of the predicted level. The one-compartment open linear pharmacokinetic calculations can be used to adequately predict serum gentamicin levels. In patients with changing or diminished renal function, pharmacokinetic predictions may not be accurate, and actual serum level determinations may be needed to monitor gentamicin therapy.