Clinical pharmacokinetics of mycophenolate mofetil

The pharmacokinetics of the immunosuppressant mycophenolate mofetil have been investigated in healthy volunteers and mainly in recipients of renal allografts. Following oral administration, mycophenolate mofetil was rapidly and completely absorbed, and underwent extensive presystemic de-esterification. Systemic plasma clearance of intravenous mycophenolate mofetil was around 10 L/min in healthy individuals, and plasma mycophenolate mofetil concentrations fell below the quantitation limit (0.4 mg/L) within 10 minutes of the cessation of infusion. Similar plasma mycophenolate mofetil concentrations were seen after intravenous administration in patients with severe renal or hepatic impairment, implying that the de-esterification process had not been substantially affected. Mycophenolic acid, the active immunosuppressant species, is glucuronidated to a stable phenolic glucuronide (MPAG) which is not pharmacologically active. Over 90% of the administered dose is eventually excreted in the urine, mostly as MPAG. The magnitude of the MPAG renal clearance indicates that active tubular secretion of MPAG must occur. At clinically relevant concentrations, mycophenolic acid and MPAG are about 97% and 82% bound to albumin, respectively. MPAG at high (but clinically realisable) concentrations reduced the plasma binding of mycophenolic acid. The mean maximum plasma mycophenolic acid concentration (Cmax) after a mycophenolate mofetil 1 g dose in healthy individuals was around 25 mg/L, occurred at 0.8 hours postdose, decayed with a mean apparent half-life (t1/2) of around 16 hours, and generated a mean total area under the plasma concentration-time curve (AUC infinity) of around 64 mg.h/L. Intra- and interindividual coefficients of variation for the AUC infinity of the drug were estimated to be 25% and 10%, respectively. Intravenous and oral administration of mycophenolate mofetil showed statistically equivalent MPA AUC infinity values in healthy individuals. Compared with mycophenolic acid, MPAG showed a roughly similar Cmax about 1 hour after mycophenolic acid Cmax, with a similar t1/2 and an AUC infinity about 5-fold larger than that for mycophenolic acid. Secondary mycophenolic acid peaks represent a significant enterohepatic cycling process. Since MPAG was the sole material excreted in bile, entrohepatic cycling must involve colonic bacterial deconjugation of MPAG. An oral cholestyramine interaction study showed that the mean contribution of entrohepatic cycling to the AUC infinity of mycophenolic acid was around 40% with a range of 10 to 60%. The pharmacokinetics of patients with renal transplants (after 3 months or more) compared with those of healthy individuals were similar after oral mycophenolate mofetil. Immediately post-transplant, the mean Cmax and AUC infinity of mycophenolic acid were 30 to 50% of those in the 3-month post-transplant patients. These parameters rose slowly over the 3-month interval. Slow metabolic changes, rather than poor absorption, seem responsible for this nonstationarity, since intravenous and oral administration of mycophenolate mofetil in the immediate post-transplant period generated comparable MPA AUC infinity values. Renal impairment had no major effect on the pharmacokinetic of mycophenolic acid after single doses of mycophenolate mofetil, but there was a progressive decrease in MPAG clearance as glomerular filtration rate (GFR) declined. Compared to individuals with a normal GFR, patients with severe renal impairment (GFR 1.5 L/h/1.73m2) showed 3-to 6-fold higher MPAG AUC values. In rental transplant recipients during acute renal impairment in the early post-transplant period, the plasma MPA concentrations were comparable to those in patients without renal failure, whereas plasma MPAG concentrations were 2- to 3-fold higher. Haemodialysis had no major effect on plasma mycophenolic acid or MPAG. Dosage adjustments appear to not be necessary either in renal impairment or during dialysis. (ABSTRACT TRUN     

Effective shelf-life of prepared sodium hypochlorite solution

Although the tissue solvent and bactericidal properties of sodium hypochlorite are well known, the effective shelf-life of prepared sodium hypochlorite solutions is not known. The stability of sodium hypochlorite is adversely affected by exposure to high temperature, light, air, and the presence of organic and inorganic contaminants. The purpose of this study was to investigate the variables of storage conditions and time on the tissue-dissolving capacity of three different concentrations of sodium hypochlorite. Fresh frozen human umbilical cord was used as the tissue sample for this experiment. Tissue samples were dissolved at time intervals ranging from 1 day to 10 wk in 5.25%, 2.62%, and 1.0% solutions of sodium hypochlorite. The tissue-dissolving ability of 5.25% sodium hypochlorite remains stable for at least 10 wk. The tissue-dissolving ability of 2.62% and 1.0% sodium hypochlorite remains relatively stable for 1 wk after mixing, then exhibits a significant decrease in tissue-dissolving ability at 2 wk and beyond.     

A study on microstructure and properties of calcium phosphate coatings processed using ion beam assisted deposition on heated substrates

In this study a set of thin Hydroxyapatite (HA) [Ca₁₀(PO₄)₆(OH)₂] coatings was deposited on heated silicon and titanium substrates using Ion Beam Assisted Deposition (IBAD). The effects of substrate temperature and processing parameters on the microstructural properties and composition of the coatings are being studied. Analytical techniques include transmission electron microscopy (TEM), scanning transmission electron microscopy (STEM) with an energy dispersive X-ray spectroscopy (EDS), as well as scanning electron microscopy (SEM) with EDX, X-ray diffraction (XRD), and Fourier Transform Infrared Spectroscopy (FTIR). The current results indicate that as substrate temperature increases the Ca/P ratio of the coatings both on titanium and silicon substrates increases. The crystallinity of the coatings and the number of calcium phosphate compounds within the coating including HA also increases. STEM-EDS revealed an atomically diffused intermediate layer at the interface between the coating and substrate. XRD results along with TEM selected area diffraction (SAD) revealed that the coatings are composed of HA, other calcium phosphate, and calcium oxide compounds.     

Implant-supported prostheses for treatment of adults with cleft palate

Six adult patients with cleft palate, ranging in age from 47 to 78 years, were treated with self-tapping titanium implants. Twenty-three implants, 7 to 15 mm in length, were placed. Of these, one (4%) was 7 mm, eight (35%) were 10 mm, nine (39%) were 13 mm, and five (22%) were 15 mm. Time between stage I and stage II implant surgeries was 5 to 14 months, averaging 8.3 months. Time from stage II surgery to the present is 1.5 to 5 years, averaging 3 years. Of the 23 implants placed, 21 (91%) achieved osseointegration. One (4%) implant was not used prosthetically. Two (9%) 10 mm implants failed to integrate in one patient. All patients were treated with a maxillary complete denture or overdenture. Five (83%) required the addition of a pharyngeal section for speech enhancement.