PMID- 10582871
OWN - NLM
STAT- MEDLINE
DCOM- 20000121
LR  - 20181113
IS  - 0066-4804 (Print)
IS  - 0066-4804 (Linking)
VI  - 43
IP  - 12
DP  - 1999 Dec
TI  - Pharmacokinetics of [(14)C]abacavir, a human immunodeficiency virus type 1
      (HIV-1) reverse transcriptase inhibitor, administered in a single oral dose to
      HIV-1-infected adults: a mass balance study.
PG  - 2855-61
AB  - Abacavir (1592U89) ((-)-(1S,
      4R)-4-[2-amino-6-(cyclopropylamino)-9H-purin-9-yl]-2-cyclopentene- 1-m ethanol)
      is a 2'-deoxyguanosine analogue with potent activity against human
      immunodeficiency virus (HIV) type 1. To determine the metabolic profile, routes
      of elimination, and total recovery of abacavir and metabolites in humans, we
      undertook a phase I mass balance study in which six HIV-infected male volunteers 
      ingested a single 600-mg oral dose of abacavir including 100 microCi of
      [(14)C]abacavir. The metabolic disposition of the drug was determined through
      analyses of whole-blood, plasma, urine, and stool samples, collected for a period
      of up to 10 days postdosing, and of cerebrospinal fluid (CSF), collected up to 6 
      h postdosing. The radioactivity from abacavir and its two major metabolites, a
      5'-carboxylate (2269W93) and a 5'-glucuronide (361W94), accounted for the
      majority (92%) of radioactivity detected in plasma. Virtually all of the
      administered dose of radioactivity (99%) was recovered, with 83% eliminated in
      urine and 16% eliminated in feces. Of the 83% radioactivity dose eliminated in
      the urine, 36% was identified as 361W94, 30% was identified as 2269W93, and 1.2% 
      was identified as abacavir; the remaining 15.8% was attributed to numerous trace 
      metabolites, of which <1% of the administered radioactivity was 1144U88, a minor 
      metabolite. The peak concentration of abacavir in CSF ranged from 0.6 to 1.4
      microg/ml, which is 8 to 20 times the mean 50% inhibitory concentration for HIV
      clinical isolates in vitro (0.07 microg/ml). In conclusion, the main route of
      elimination for oral abacavir in humans is metabolism, with <2% of a dose
      recovered in urine as unchanged drug. The main route of metabolite excretion is
      renal, with 83% of a dose recovered in urine. Two major metabolites, the
      5'-carboxylate and the 5'-glucuronide, were identified in urine and, combined,
      accounted for 66% of the dose. Abacavir showed significant penetration into CSF.
FAU - McDowell, J A
AU  - McDowell JA
AD  - Glaxo Wellcome, Inc., Research Triangle Park, North Carolina 27709, USA.
      JAM36914@glaxowellcome.com
FAU - Chittick, G E
AU  - Chittick GE
FAU - Ravitch, J R
AU  - Ravitch JR
FAU - Polk, R E
AU  - Polk RE
FAU - Kerkering, T M
AU  - Kerkering TM
FAU - Stein, D S
AU  - Stein DS
LA  - eng
PT  - Clinical Trial
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Antimicrob Agents Chemother
JT  - Antimicrobial agents and chemotherapy
JID - 0315061
RN  - 0 (Anti-HIV Agents)
RN  - 0 (Dideoxynucleosides)
RN  - 0 (Reverse Transcriptase Inhibitors)
RN  - EC 2.7.7.49 (HIV Reverse Transcriptase)
RN  - WR2TIP26VS (abacavir)
SB  - IM
SB  - X
MH  - Adult
MH  - Anti-HIV Agents/administration & dosage/cerebrospinal fluid/*pharmacokinetics
MH  - Chromatography, High Pressure Liquid
MH  - Dideoxynucleosides/administration & dosage/cerebrospinal fluid/*pharmacokinetics
MH  - Feces/chemistry
MH  - HIV Infections/*metabolism
MH  - HIV Reverse Transcriptase/*antagonists & inhibitors
MH  - *HIV-1
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Reverse Transcriptase Inhibitors/administration & dosage/cerebrospinal
      fluid/*pharmacokinetics
MH  - Spectrophotometry, Ultraviolet
PMC - PMC89576
EDAT- 1999/12/03 00:00
MHDA- 1999/12/03 00:01
CRDT- 1999/12/03 00:00
PHST- 1999/12/03 00:00 [pubmed]
PHST- 1999/12/03 00:01 [medline]
PHST- 1999/12/03 00:00 [entrez]
PST - ppublish
SO  - Antimicrob Agents Chemother. 1999 Dec;43(12):2855-61.