PMID: 9661027Jul 14, 1998Paper

Pharmacokinetics of the protease inhibitor KNI-272 in plasma and cerebrospinal fluid in nonhuman primates after intravenous dosing and in human immunodeficiency virus-infected children after intravenous and oral dosing

Antimicrobial Agents and Chemotherapy
B U MuellerF M Balis

Abstract

KNI-272 is a human immunodeficiency virus (HIV) protease inhibitor with potent activity in vitro. We studied the pharmacokinetics of KNI-272 in the plasma and cerebrospinal fluid (CSF) of a nonhuman primate model and after intravenous and oral administration to children with HIV infection. Plasma and CSF were sampled over 24 h after the administration of an intravenous dose of 50 mg of KNI-272 per kg of body weight (approximately 1,000 mg/m2) to three nonhuman primates. The pharmacokinetics of KNI-272 were also studied in 18 children (9 males and 9 females; median age, 9.4 years) enrolled in a phase I trial of four dose levels of KNI-272 (100, 200, 330, and 500 mg/m2 per dose given four times daily). The plasma concentration-time profile of KNI-272 in the nonhuman primate model was characterized by considerable interanimal variability and rapid elimination (clearance, 2.5 liters/h/kg; terminal half-life, 0.54 h). The level of drug exposure achieved in CSF, as measured by the area under the KNI-272 concentration-time curve, was only 1% of that achieved in plasma. The pharmacokinetics of KNI-272 in children were characterized by rapid elimination (clearance, 276 ml/min/m2; terminal half-life, 0.44 h), limited (12%) and apparently...Continue Reading

References

Dec 1, 1979·Computer Programs in Biomedicine·G D Knott
Jan 1, 1992·The Journal of Infectious Diseases·F M BalisP Jarosinski
Feb 15, 1989·Annals of Internal Medicine·F M BalisD G Poplack
Jul 1, 1988·Proceedings of the National Academy of Sciences of the United States of America·N E KohlI S Sigal
Dec 7, 1995·The New England Journal of Medicine·M MarkowitzJ M Leonard
Jun 1, 1995·Antimicrobial Agents and Chemotherapy·M E HawkinsF M Balis
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Feb 1, 1995·Journal of Pharmaceutical Sciences·T O CarpenterJ Pitha
Apr 26, 1994·Proceedings of the National Academy of Sciences of the United States of America·J P VaccaE Roth
Dec 1, 1995·Antimicrobial Agents and Chemotherapy·S M BlaneyF M Balis

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