Dose proportionality of stavudine in hiv seropositive asymptomatic subjects: Application to bioequivalence assessment of various capsule formulations
✍ Scribed by Sanjeev Kaul; Vanaja Mummaneni; Rashmi H. Barbhaiya
- Book ID
- 102758652
- Publisher
- John Wiley and Sons
- Year
- 1995
- Tongue
- English
- Weight
- 658 KB
- Volume
- 16
- Category
- Article
- ISSN
- 0142-2782
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✦ Synopsis
The dose proportionality and bioequivalence of the capsule formulations used in clinical trials and the proposed commercial formulations of stavudine were assessed in an openlabel, single-dose, randomized four-way crossover study in 16 asymptomatic HIVinfected males. One capsule of stavudine (5, 10, 20, or 40 mg) was administered orally to each subject in each of the four treatment periods. Serial blood samples were collected for 10 h after each dose and the plasma was assayed for intact stavudine by a validated radioimmunoassay method. The plasma concentration-time data were subjected to noncompartmental pharmacokinetic analysis. For doses ranging from 5 to 40 mg, mean C,,, and AUC,, values were in the range of 110.36-889.34ng mL-' and 246.46-1945.97 h ng mL-' respectively. The mean C,,, and AUC,, of stavudine increased in a dose-proportional manner. Irrespective of the dose, mean C , , , values were observed at a median tmax of 0.75 h or less. Mean t,,* values were 1.97, 1.77, 1.67 and 1.66 h for the 5, 10, 20, and 40 mg capsules, respectively. For bioequivalence assessment, C,,, and AUC,, values were normalized to the lOmg dose since these parameters were dose proportional. The 10 mg capsule formulation used in phase-3 clinical trials was chosen as the reference. The relative bioavailability estimates and 90% confidence limits for the dose-normalized C, , , values with the lOmg capsule as the reference were 86% (76%, 96%), 99% (88%, IlOYo), and 90% (SOY0, IOOYO) for the 5, 20, and 40mg capsules, respectively. The differences in the point estimates of the dose-normalized AUC,, values for the 5, 20, and 40 mg capsules relative to the 10 mg phase-3 capsule were 1 YO or less, and the 90% confidence limits were all within 95-106%. These results indicate that stavudine exhibits linear pharmacokinetics and that the 5, 10, 20, and 40mg capsules of stavudine are bioequivalent.