Population pharmacokinetics of atorvastatin, simvastatin and pravastatin after oral administration in humans

The purpose of this study is to determine the population pharmacokinetics of 3 statins after oral dosing. This was achieved by simultaneous data fitting of 101 different individuals from three studies: 25 subjects for pravastatin, 40 subjects for simvastatin and 36 subjects for atorvastatin. Each study was fitted separately. Plasma profiles were best characterized by 1 -compartment model for pravastatin, 2-compartment model for simvastatin, and 3 -compartment model for atorvastatin. The criteria used for model building involved the examination of the fitted cuves, the improvement in objective function and statistical tests: Akaike test, Schwarz test and log likelihood test; and examining the improvement in residual plots. The elimination rate constant and clearance values for pravastatin is higher than simvastatin and higher than atorvastatin which is in agreement with models used. The variability, as indicated by population coefficient of variation, is generally higher than 30% rendering them highly variable drugs

Pharmacokinetics and bioavailability of doxycycline in ostriches (Struthio camelus) at two different dose rates

A bioavailability and pharmacokinetics study of doxycycline was carried out on 30 healthy ostriches after a single intravenous (IV), intramuscular (IM) and oral dose of 15 mg/kg body weight. The plasma doxycycline concentration was determined by HPLC/UV at 0 (pretreatment), 0.08, 0.25, 0.5 1, 2, 4, 6, 8, 12, 24 and 48 h after administration. The plasma concentration-time curves were examined using non-compartmental methods based on the statistical moment theory for only the higher dose. After IV administration, the elimination half-life (t(1/2beta)), mean residence time (MRT), volume of distribution at the steady-state (V(ss)), volume of distribution (Vd(area)) and total body clearance (Cl(B)) were 7.67 +/- 0.62 h, 6.68 +/- 0.86 h, 0.86 +/- 0.16 l/kg, 1.67 +/- 0.52 l/kg and 2.51 +/- 0.63 ml/min/kg, respectively. After IM and oral dosing, the mean peak plasma concentrations (C(max)) were 1.34 +/- 0.33 and 0.30 +/- 0.04 microgram/ml, respectively, which were achieved at a postadministration time (t(max)) of 0.75 +/- 0.18, 3.03 +/- 0.48 h, respectively. The t(1/2beta), Vd(area) and Cl(B) after IM administration were 25.02 +/- 3.98 h, 23.99 +/- 3.4 l/kg and 12.14 +/- 1.71 ml/min/kg, respectively and 19.25 +/- 2.53 h, 61.49 +/- 7 l/kg and 40.19 +/- 3.79 ml/min/kg after oral administration, respectively. The absolute bioavailability (F) of doxycycline was 5.03 and 17.52% after oral and IM administration, respectively. These results show that the dose data from other animals particularly mammals cannot be extrapolated to ostriches. Therefore, based on these results along with those reported in the literature, further studies on the pharmacokinetic/pharmacodynamic, in vitro minimum inhibitory concentration values and clinical applications of doxycycline in ostriches are required.

Evaluation of hydroxyethyldiclofenac intestinal absorption in rats

The mechanism of intestinal mucosal transport of hydroxyethyldiclofcnac, an ester prodrug of diclofenac, in rats was investigated. Another objective was to identify optimal sites of absorption and then to identify the gastrointestinal toxicity. Both the parent drug and the prodrug were found to be passively absorbed from rat jejunum. The permeability coefficients of the prodrug were tenfold higher [p<0.05] than that of the parent drug in the three regions of rat small intestine [duodenum, jejunum and ileum]. In addition, the prodrug was found to be less ulcerogenic [p<0.05] after single and chronic dose than the parent drug. In conclusion, the prodrug was found a good candidate for oral delivery as compared to parent compound