Accuracy of estimated creatinine clearance in obese patients with stable renal function in the intensive care unit

We compared agreement between creatinine clearance values in obese, critically ill patients calculated using three common empirically derived formulas and modifications thereof, with creatinine clearance obtained by conventional 24-hour urine collection. We selected the charts of 22 patients in intensive care units (86% medical, 14% surgical) according to the following criteria: actual body weight greater than 150% of ideal body weight; serum creatinine variation of less than 15% from the day of starting 24-hour urine collection to the day before or after the collection; presence of a urinary bladder catheter; no history of renal dialysis; and clinical indication for renal function assessment. Mean measured 24-hour urinary creatinine clearance for all patients was 72 +/- 64 ml/minute (range 8-248 ml/min). The method of estimating creatinine clearance that showed the least mean bias was the equation of Salazar and Corcoran using a corrected serum creatinine concentration (mean bias -2 ml/min); however, the corresponding 95% confidence intervals were wide (-133-129 ml/min). The narrowest range of 95% confidence intervals were seen with Jelliffe's equation (mean bias 25 ml/min, 95% confidence intervals -41-90 ml/min). In this sample, estimated creatinine clearances did not agree acceptably with measured values. Despite low mean bias values, none of the empirically derived equations that we studied had clinically acceptable 95% confidence intervals. We recommend using the 24-hour urine collection method when assessing creatinine clearance in obese, critically ill patients.     

Dynamic dialysis method. III. Effect of sulfonamides on the binding of warfarin with bovine serum albumin

Enflurane, a fluorinated methylethyl ether, is metabolized, in part, to inorganic fluoride. Methoxyflurane has similar metabolism, and cases of fluoride ion-induced renal failure have been reported after its use. This prospective study was initiated to determine fluoride ion kinetics after enflurance anesthesia in 16 healthy patients, 18 anephric patients, and 6 patients each having a creatinine clearance of less than 5 ml/min (on dialysis). Serum and urine inorganic fluoride levels were determined. There was no clinical or statistical significance difference among the 3 groups with respect to maximum inorganic fluoride ion concentration or the time to reach it. The fluoride ion values were never above the 50 muM level that has been reported to cause subclinical renal toxicity. The fluoride ion concentration in serum fell rapidly after termination of anesthesia even in the anephric patients. This is presumed to be due to uptake of the ion by bone. Patients with low creatinine clearance also have low fluoride ion clearance. Statistical but not clinical significance was found in the comparison between pre-enflurane and the 24-hr fluoride ion values in the anephric and low creatine clearance patients, but this did not persist after one dialysis.     

Close correlation between visceral fat accumulation and uric acid metabolism in healthy men

We evaluated the effect of accumulation of intraabdominal visceral fat on the metabolism of uric acid in 50 healthy male subjects to elucidate any relationship between such obesity and hyperuricemia. The area of abdominal fat (visceral fat and subcutaneous fat) was measured at the level of the umbilicus by abdominal computed tomographic scanning. Serum and urinary concentrations of uric acid and creatinine were determined with an autoanalyzer. Uric acid clearance and the ratio of urinary uric acid to creatinine excreted in urine were calculated. Univariate and multivariate analyses were used to evaluate the relationship between uric acid metabolism and body fat. The size of the area of visceral fat was significantly correlated with the serum concentration of uric acid (r = .37, P < .01), uric acid clearance (r = -.34, P < .05), and the urinary uric acid to creatinine ratio (r = .65, P < .0001). The size of the area of subcutaneous fat was significantly correlated only with the urinary uric acid to creatinine ratio (r = .38, P < .01). Multivariate analyses, including body mass index (BMI), showed that the size of the visceral fat area was the strongest contributor to an elevated serum concentration of uric acid, a decrease in uric acid clearance, and an increase in the urinary uric acid to creatinine ratio. These results suggest that accumulation of visceral fat may have a greater adverse effect on the metabolism of uric acid than BMI or accumulation of subcutaneous fat. Clearly, patients with hyperuricemia should lose weight to reduce excessive visceral fat stores, to help avoid attacks of gout.     

The motor organization of the sense of rhythm

Serum inorganic fluoride levels in obese versus control patients were compared during and after sevoflurane anesthesia. Mean serum inorganic fluoride levels in the obese group increased more rapidly and were significantly higher than in the control group at each sampling time (P < 0.01). The area under the curve of fluoride concentration, versus time up to 24 h and 48 h in the obese patients, was significantly greater than that in the nonobese patients (P < 0.001). Peak serum fluoride level in the obese patients was 51.7 +/- 2.5 mumol/L and exceeded 50 mumol/L for nearly 2 h. Our study showed that serum fluoride concentrations between mildly obese and nonobese patients differed during and after sevoflurane anesthesia.     

Renal function in patients during and after hypotensive anesthesia with sevoflurane

STUDY OBJECTIVES: To evaluate renal function during and after hypotensive anesthesia with sevoflurane compared with isoflurane in the clinical setting. DESIGN: Randomized, prospective study. SETTING: Inpatient surgery at Rosai Hospital. PATIENTS: 26 ASA physical status I and II patients scheduled for orthopedic surgery. INTERVENTIONS: Patients received isoflurane, nitrous oxide (N2O), and fentanyl (Group I = isoflurane group; n = 13) or sevoflurane, N2O, and fentanyl (Group S = sevoflurane group; n = 13). Controlled hypotension was induced with either isoflurane or sevoflurane to maintain mean arterial pressure at 60 mmHg for 120 minutes. MEASUREMENTS AND MAIN RESULTS: Measurements included serum inorganic fluoride (previously speculated to influence renal function), creatinine clearance (CCr; to assess renal glomerular function), urinary N-acetyl-beta-D-glucosaminidase (NAG; to assess renal tubular function), blood urea nitrogen (BUN), and serum creatinine (as clinical renal function indices). Serum fluoride, CCr, and NAG were measured before hypotension, 60 minutes, and 120 minutes after the start of hypotension, 30 minutes after recovery of normotension, and on the first postoperative day. BUN and serum creatinine were measured preoperatively and on the third and seventh postoperative days. Minimum alveolar concentration times hour was 3.6 +/- 1.8 in Group I and 4.0 +/- 0.7 in Group S. In both groups, BUN and serum creatinine did not change, and CCr significantly decreased after the start of hypotension. In Group I, serum fluoride and NAG did not change. In Group S, serum fluoride significantly increased after the start of hypotension compared with prehypotension values and compared with Group I values. In addition, NAG significantly increased at 120 minutes after the start of hypotension and at 30 minutes after recovery of normotension, but returned to prehypotension values on the first postoperative day. CONCLUSIONS: Two hours of hypotensive anesthesia with sevoflurane under 5 L/min total gas flow in patients having no preoperative renal dysfunction transiently increased NAG, which is consistent with a temporary, reversible disturbance of renal tubular function.     

Ogilvie''s syndrome: a new approach to an old problem

The effect of glucose infusion on renal handling of purine bases and oxypurinol was examined in 6 normal subjects. Five hundred milliliters of 1.1 M glucose solution were administered intravenously in 1 h. Fractional clearances of uric acid, xanthine and oxypurinol were significantly increased during glucose infusion, but that of hypoxanthine was not changed, while a 1-hour infusion of 500 ml of 1.1 M mannitol had no effect on the fractional clearances of purine bases and oxypurinol. These data indicate that the effect of glucose infusion on the renal clearances of uric acid, xanthine and oxypurinol was not related to osmotic diuresis but induced by glycosuria and/or hyperglycemia. Accordingly, the glycosuria- and/or hyperglycemia-induced decrease in the biological half-life of oxypurinol must be considered in the administration of allopurinol to gouty patients with uncontrolled diabetes mellitus.     

Incidence and magnitude of hypoxaemia with ketamine in a rural African hospital

The excretion of sevoflurane metabolites in the urine collected every 12 h after sevoflurane anaesthesia was measured by ion exchange chromatography. A metabolite, which was converted on incubation with glucuronidase to hexafluoroisopropanol was detected in the urine. The maximum excretion was found in the first 12 h after anaesthesia, none was found in the last collection 3 days after anaesthesia. The excretion half-life for the metabolite was calculated to be 55 h. A significant increase in the urinary excretion of organic and inorganic fluoride was also observed during the first 12 h after anaesthesia. The cumulative organic and inorganic fluoride excretion in the 3 days after sevoflurane anaesthesia was 1588 and 856 mumol, respectively (ratio = 1.85). The excreted half-lives for organic and inorganic fluoride were calculated to be 4028 and 2069 min, respectively. Our study showed that a hexafluoroisopropanol glucuronide is excreted in the urine, and the major part of urinary metabolites of sevoflurane, organic and inorganic fluoride, are excreted within 2 days of sevoflurane inhalation in man.     

Effect of large oral doses of ascorbic acid on uric acid excretion by normal subjects

The effects of large and oral doses of ascorbic acid on renal clearance and excretion of uric acid were studied in nongouty subjects because ascorbic acid has been reported to increase renal uric acid clearance. Our results indicate that 4 or 12 gm ascorbic acid taken in divided doses had no effect on serum uric acid concentration or uric acid excretion and clearance by the kidney. Reasons for these results, which differ from previous reports, are discussed. We quantitated the magnitude of the interference of ascorbic acid in the measurement of uric acid by the nonspecific methods frequently used, since falsely elevated urine uric acid could lead to misinterpretation of screening tests.     

Influence of sevoflurane and isoflurane anesthesia on renal function in elderly patients

We examined the influence of sevoflurane and isoflurane anesthesia on renal function in elderly patient who underwent gastrectomy. Plasma inorganic fluoride level was significantly higher in sevoflurane group compared with isoflurane group from 3 hours after the beginning of anesthesia to the 3rd operative day. In contrast, parameters such as urinary beta 2 microglobulin, urinary N-acetyl-beta-D-glucosaminidase, and urinary gamma-GTP activities increased in both groups, but the increase was not significant. Serum BUN and creatinine levels were within normal limits. These results suggest that elderly patients without renal dysfunction appear unlikely to have any significant problem after prolonged sevoflurane anesthesia.     

Role of the kidneys in the metabolism of furosemide: its inhibition by probenecid

The site where furosemide is metabolized and the location where probenecid reduces furosemide metabolism remain poorly defined. The liver appears to play a minor role, and there is indirect evidence suggesting that the kidneys could be responsible for the metabolism of furosemide. To assess the role of the kidneys in the metabolism of furosemide, its intravenous kinetics have been studied in control and anephric rabbits, after the ligation of the renal pedicles. Two additional groups of rabbits, control and anephric, have received probenecid before the administration of furosemide. In the control group, the total clearance of furosemide was 18.65 +/- 1.01 mL/ min per kg; urinary and metabolic clearances of furosemide were 7.95 +/- 0.65 and 10.70 +/- 1.11 mL/min per kg, respectively. In anephric rabbits, total clearance was reduced by 85% to 2.69 +/- 0.26 mL/min per kg (P < 0.001), secondary to the abolition of furosemide renal excretion and to the reduction in metabolic clearance from 10.70 +/- 1.11 to 2.69 +/- 0.26 mL/min per kg (P < 0.001). The pretreatment with probenecid reduced the total clearance of furosemide by 80%, to 3.62 +/- 0.24 mL/min per kg (P < 0.001), because of a reduction of 90 and 75% in urinary and metabolic clearances, respectively. The administration of probenecid to anephric rabbits did not reduce further the metabolic clearance. It is concluded that the kidneys are responsible for 85% of furosemide total clearance, either via excretion (43%) or biotransformation (42%), and that probenecid inhibits both processes.     

Organisation of the bph gene cluster of transposon Tn4371, encoding enzymes for the degradation of biphenyl and 4-chlorobiphenyl compounds

We have isolated beta-trace protein from cerebrospinal fluid, serum, plasma, and urine samples of normal volunteers and sera and hemofiltrate of patients with chronic renal failure. Blood-derived and urinary beta-trace have significantly higher molecular weights than their cerebrospinal fluid counterpart, the amino acid sequences being identical. Oligosaccharide structural analysis revealed these molecular weight differences to be due to different N-glycosylation. beta-Trace from hemofiltrate and urine has larger sugar chains and concurrently significantly higher sialylation than cerebrospinal fluid-beta-trace which bears truncated "brain-type" oligosaccharide chains (published previously). beta-Trace concentrations were about 40 ng/ml for normal sera and plasma. 2000-6000 ng/ml were measured in sera of dialysis patients whereas in normal human cerebrospinal fluid, beta-trace concentration was about 8000 ng/ml. A reduced amount of 900 ng/ml was found in a single case of hydrocephalus cerebri. The sialylated glycoforms of beta-trace detected in the blood are presumably derived from resorbed cerebrospinal fluid protein whereas beta-TP-molecules bearing asialo-oligosaccharides are absent due to their hepatic clearance. The residual, sialylated beta-TP-species are probably eliminated from the blood via the kidney. This physiological clearance mechanism for the sialylated glycoforms is disturbed in hemodialysis patients resulting in about 100-fold elevated serum concentrations. These results let us suggest beta-trace may become a useful novel diagnostic protein in renal diseases.     

Long-term nephrotoxicity of cisplatin, ifosfamide, and methotrexate in osteosarcoma

The acute renal effects of chemotherapy are known, but long-term nephrotoxicity has rarely been investigated. The aim of the present study was to assess long-term renal function in children and adolescents who received at-risk chemotherapy, including cisplatin, ifosfamide, and methotrexate, to treat an osteosarcoma. Renal function tests [creatinine clearance, microalbuminuria, and renal excretion of sodium, potassium, chloride, calcium, magnesium (Mg), phosphorus (P), and uric acid] were prospectively performed 5.4+/-2.2 (+/-SD) years after chemotherapy (total cumulative dose: methotrexate 41+/-31 g/m2, ifosfamide 39+/-14 g/m2, cisplatin 674+/-188 mg/m2) in 18 children and adolescents. The results were compared with 13 normal volunteers matched for age and sex. Creatinine clearance, which was greater than 80 ml/min per 1.73 m2 in all patients, correlated with the total dose of ifosfamide (r=0.55, P<0.05) and cisplatin (r=0.48, P<0.05). Microalbuminuria was noted in 4 patients. Hypomagnesemia was present in 4 and hypercalciuria in 3 patients; renal excretion of P, Mg, and uric acid was higher in patients than in controls. Glomerular function was not significantly altered and only mild tubular dysfunction was present. Since renal excretion of P and Mg were increased in patients compared with normal volunteers and hypercalciuria was occasionally seen, divalent ion disorders are the most-likely potential complications.     

Clearance of iohexol, chromium-51-ethylenediaminetetraacetic acid, and creatinine for determining the glomerular filtration rate in pigs with normal renal function: comparison of different clearance techniques

RATIONALE AND OBJECTIVES: We wanted to improve determination of the glomerular filtration rate (GFR) with plasma clearance techniques because the alternative-renal clearance techniques-may involve inaccurate urine sampling or risk of urinary tract infection when bladder catheterization becomes necessary. Therefore, we compared the renal and plasma clearances of iohexol and chromium-51-ethylenediaminetetraacetic acid (51Cr-EDTA), as well as endogenous creatinine clearance, in 19 normal pigs using different techniques. METHODS: After an intravenous bolus injection of the GFR markers, 16 plasma samples were used to plot the marker concentrations versus time for 4.5 hr. Urine was collected during nine 30-min periods. Plasma clearance was calculated by dividing the dose of marker with the area under the plasma concentration curve (AUC) from the time of injection to infinity using one-compartment (ClAUC-slope) and three-compartment (ClAUC-3comp) models. The renal clearance was calculated by dividing the amount of marker excreted in the urine in a period with the AUC in the same period. This AUC was determined by integrating the total area in the period (Clren adv)--our reference method representing the "true" GFR--or by using the arithmetic mean of the plasma concentrations of the marker at the beginning and end of the urine collection period (Clren simple). Creatinine clearance was determined according to Clren simple. RESULTS: Renal clearances of iohexol and 51Cr-EDTA were significantly higher than creatinine clearance (P = .0002). There was no significant difference between the renal clearances of iohexol and 51Cr-EDTA or between their plasma clearances. The two mathematical methods of calculating the renal clearance of iohexol were highly correlated (rs = .99), as were the two methods of calculating its plasma clearance (rs = .95). Because of the extrarenal clearance of the markers, the plasma clearance methods for iohexol and 51Cr-EDTA always overestimated the true GFR. ClAUC-3comp was the method closest to the true GFR. For iohexol, the median overestimation of the GFR was higher with ClAUC-slope when early plasma samples (30-120 min) after injection of the marker were used (5.5 ml.min-1.10 kg-1) than when late samples (180-270 min) were used (4.0 ml.min-1.10 kg-1). After subtracting the median extrarenal clearances of iohexol and 51Cr-EDTA (previously determined in nephrectomized pigs) from their plasma clearances (ClAUC-3comp), the median overestimation of the true GFR was reduced from 2.0 to 1.1 ml.min-1.10 kg-1 with iohexol and from 2.1 to 1.3 ml.min-1.10 kg-1 with 51Cr-EDTA. CONCLUSION: GFR determination with plasma clearance techniques can be improved in three- and one-compartment models by taking late plasma samples and by subtracting the extrarenal plasma clearance of the species. One-compartment models can be improved by determining a correction formula in the species for the early parts of the decay curve of the plasma concentration of the marker.     

Renal clearance of digoxin in premature neonates

The renal clearances of digoxin and creatinine were determined in seven premature neonates (mean gestational age = 29.9 wk, range = 26 to 36 wk) at a postnatal age of 1 to 9 days (mean = 4.1 days). The corrected renal digoxin clearance (mean, 10.4 ml/min/1.73 m2; range, 2.5 to 36.7) was highly dependent on gestational age and body weight, r being 0.95 and 0.96, respectively (exponential curve). The linear slope of corrected renal digoxin clearance vs. creatinine clearance plot approached unity (r = 0.99), indicating that digoxin and creatinine were handled similarly by the kidney in these premature neonates (i.e. glomerular filtration with some degree of tubular secretion). Our finding of slower renal digoxin clearance helps to explain the higher serum levels and longer half-life of this drug in premature neonates.     

Mechanisms of elevation of serum and urinary concentrations of soluble thrombomodulin in diabetic patients: possible application as a marker for vascular endothelial injury

Serum and urinary levels of soluble thrombomodulin (TM) were measured in 71 patients with non-insulin-dependent diabetes mellitus (NIDDM) and 132 age-matched control subjects to elucidate the mechanisms involved in increased TM levels. We compared the TM level with urinary albumin excretion (UAE), creatinine (Cr) clearance, and indices of renal tubular damage such as urinary beta2-microglobulin. Serum TM was significantly higher in diabetic patients versus control subjects (P < .001) regardless of whether the patients had diabetic nephropathy. Urinary TM levels were also higher in diabetic patients than in control subjects (P < .001). Serum TM in diabetic patients was correlated positively with serum Cr and UAE and inversely with the Cr clearance rate (P < .001, respectively). The urinary level of TM in diabetic patients was significantly correlated with 24-hour glucose excretion and the serum level of 1,5-anhydroglucitol (1,5-AG) (P < .001). However, no correlations were found between urinary TM levels and renal function in diabetic patients. There was also no correlation between serum and urinary levels of TM in the patients. These results suggest that although the serum TM level is influenced by an impairment of the renal clearance of TM, this parameter may be a useful marker for vascular endothelial injury in diabetic patients. On the other hand, since the elevated urinary level of TM in the patients paralleled their urinary excretion of glucose, urinary TM levels do not correlate with vascular endothelial injury in diabetic patients.     

Urinary fibrin-fibrinogen degradation products in nephrotic syndrome

The urinary concentration of fibrin-fibrinogen degradation products (F.D.P.) was measured in 90 patients with proteinuria above 2 g/1 and correlated with proteinuria, differential protein clearances, serum urea and creatinine, and renal biopsy findings. There was a linear correlation (r equals 0-7; P less than 0-001) between the urinary F.D.P. excretion and the selectivity of the proteinuria such that patients with highly selective proteinuria excreted only small amounts of F.D.P. whereas those with non-selective proteinuria excreted much higher levels. There was a significant correlation between the urinary F.D.P. excretion and the urine:serum (U:S) ratio of IgG excretion but not with the U:S ratio or urinary excretion of albumin or transferrin. Sephadex G200 column chromatography of the concentrated urine in 26 cases showed that patients with highly selective proteinuria excreted predominantly F.D.P. of low molecular weight in the urine whereas those with non-selective proteinuria excreted mainly fibrinogen and products of high molecular weight. Hence the type and quantity of F.D.P. in the urine are determined primarily by the differential filtration of fibrinogen and the various degradation products from the plasma through the glomerular basement membrane, which in turn is determined by the "pore size" of the basement membrane. In clinical nephrology measurement of the urinary F.D.P. level provides a rapid and convenient means of estimating the differential protein clearance.     

Effects of furosemide on glomerular filtration rate and clearance of practolol, digoxin, cephaloridine, and gentamicin

Furosemide was shown to decrease inulin clearance in 20 of 27 normal subjects. The depression in inulin clearance occurred in both water-loaded and non-water-loaded subjects. The renal clearance of practolol, but not digoxin, was reduced when furosemide was given. The average total plasma clearances of gentamicin and of cephaloridine over a 6-hr period were decreased after furosemide. The reduced clearances of the antibiotics were associated with higher plasma levels, the increase in antibiotic concentration being as much as 100% at 1 hr after an intravenous bolus injection.     

Changes in urinary uric acid excretion in obstructive sleep apnea before and after therapy with nasal continuous positive airway pressure

STUDY OBJECTIVE: To assess the utility of urinary uric acid excretion as a marker of nocturnal hypoxia in patients with obstructive sleep apnea-hypopnea syndrome (OSAHS) before and after the institution of nasal continuous positive airway pressure (CPAP). DESIGN: Prospective, open. SETTING: Sleep Disorders Laboratory, Veterans Affairs Medical Center. PARTICIPANTS: Thirty consecutive male subjects, 20 with OSAHS and 10 without OSAHS. MEASUREMENTS AND METHODS: Spot morning urine and venous blood samples were obtained in all subjects; samples were also obtained after the application of CPAP in those with OSAHS. Uric acid excretion, normalized to creatinine clearance, was calculated as the product of urinary uric acid and serum creatinine concentrations divided by urine creatinine concentration. In patients with OSAHS, uric acid excretion was 0.55+/-0.1 mg/dL before CPAP therapy and decreased to 0.30+/-0.01 mg/dL after CPAP therapy (p < 0.001). The latter value did not differ significantly from the mean value (0.32+/-0.03 mg/dL) in the control group. Uric acid excretion in OSAHS patients correlated significantly with the apnea-hypopnea index (r=0.42; p<0.0003). CONCLUSION: Uric acid excretion is increased in OSAHS patients and normalizes after CPAP treatment, most likely reflecting differences in tissue oxygenation between the two conditions. Further studies in large number of patients may confirm the usefulness of this simple test for diagnosis and follow-up of patients with OSAHS.     

Increase in serum creatine phosphokinase concentrations after suxamethonium during sevoflurane or isoflurane anaesthesia in children

We have studied whether sevoflurane or isoflurane anaesthesia modulates the effect of suxamethonium on serum concentrations of enzyme markers of skeletal muscle function in paediatric patients. Eighty patients undergoing bilateral tonsillectomy, aged 5-12 yr, were allocated randomly to receive anaesthesia with either sevoflurane and nitrous oxide or isoflurane and nitrous oxide. Serum creatine phosphokinase (CK), aspartate aminotransferase (AST), alanine aminotransferase (ALT) and lactate dehydrogenase (LDH) concentrations were measured before, and at 30 min and 20 h after induction of anaesthesia. Mean CK concentrations increased from 97.0 (SD 17.3) to 478 (170) iu litre-1 in the sevoflurane group and from 86.9 (22.4) to 628 (223) iu litre-1 in the isoflurane group, 20 h after induction of anaesthesia. Mean peak serum CK concentration in the sevoflurane group (478 (170) iu litre-1) was significantly less (P < 0.05) than that in the isoflurane group (628 (223) iu litre-1). Mean serum AST concentration increased from 17.5 (4.9) to 31.7 (3.5) iu litre-1 in the sevoflurane group and from 17.3 (2.4) to 34.8 (5.7) iu litre-1 in the isoflurane group, 20 h after induction of anaesthesia. Mean peak serum AST concentrations in the sevoflurane group were significantly lower (P < 0.05) than those in the isoflurane group. There were no significant differences in serum ALT or LDH concentrations between the groups either before or after anaesthesia. We conclude that administration of suxamethonium during either sevoflurane or isoflurane anaesthesia caused a marked increase in serum CK concentrations in paediatric patients. The clinical significance of this finding is uncertain.     

Interspecies scaling of renally secreted drugs

The objective of this study is to predict pharmacokinetic parameters (clearance, volume of distribution at steady state, and elimination half-life) in humans from animal data for drugs which are renally secreted in humans. Pharmacokinetic parameters of ten drugs were scaled-up from animal data obtained from the literature. Using simple allometry (pharmacokinetic parameter of interest vs body weight), total, renal and nonrenal clearances, volume of distribution and half-life were predicted in humans. The predicted parameters were compared with the observed parameters. The results of the study indicated that it is likely that the predicted total and renal clearances from animal data will be underestimated in humans for renally secreted drugs. The prediction of renal clearance was improved by normalizing the renal clearance by a 'correction factor' for animals who exhibited renal secretion. The predicted volume and half-life were comparable with the observed values in man. Overall, the results of this study indicate that caution should be employed in interpreting the total and renal clearance of renally secreted drugs predicted by the allometric approach.