COMPARATIVE-STUDY OF BIOAVAILABILITIES AND PHARMACOKINETICS OF CLINDAMYCIN IN HEALTHY-VOLUNTEERS AND PATIENTS WITH AIDS

The absolute oral bioavailability and pharmacokinetics of clindamycin administered to 16 healthy volunteers and 16 patients with AIDS were c ompared. Clindamycin was given intravenously (i.v.) (Cleocin phosphate ) at a dose of 600 mg as a 25-min infusion and orally (Cleocin hydroch loride) by use of a crossover design in both study groups. Plasma samp les were analyzed by gas-liquid chromatography. Plasma drug clearance and volume of distribution at the steady state following the i.v. dose differed between study groups. The clearances were 0.27 +/- 0.06 lite r/h/kg in healthy volunteers and 0.21 +/- 0.06 liter/h/kg in AIDS pati ents (P = 0.014; Mann-Whitney U test); the volumes of distribution at the steady state were 0.79 +/- 0.13 and 0.66 +/- 0.12 liter/kg in heal thy volunteers and AIDS patients, respectively (P = 0.005). The elimin ation half-life did not differ between the two groups. The bioavailabi lity of clindamycin capsules in AIDS patients was approximately 1.5 ti mes that in healthy volunteers (0.53 +/- 0.14 versus 0.75 +/- 0.20; P = 0.002). Peak concentrations following the oral dose were higher in A IDS patients as well (7.7 +/- 2.5 versus 5.3 +/- 1.0 mg/liter; P = 0.0 008). Three AIDS patients experienced severe diarrhea following the or al dose; four patients had mild diarrhea following the i.v. dose. No a dverse effects were reported by the healthy volunteers. The pharmacoki netic parameters observed in this study for AIDS patients may be usefu l for the consideration of clindamycin dosage regimens in patients tre ated for toxoplasmic encephalitis. These findings suggest that the eff ect of AIDS on drug disposition deserves further investigation, partic ularly for orally administered drugs.