The safety and pharmacokinetics of a reverse transcriptase inhibitor, 3TC, in patients with HIV infection: a phase I study.
OBJECTIVE
To determine the safety and pharmacokinetics of the nucleoside analogue, 3TC.


METHODS
A Phase I, open-label, single-centre study.


METHODS
Twenty asymptomatic, HIV-infected male patients with CD4 lymphocyte counts < 500 x 10(6)/l who had not received previous antiretroviral therapy completed the study. Each patient received a single intravenous dose followed by a single oral dose of 3TC. Four patients were dosed at each of five dose levels (0.25, 1.0, 2.0, 4.0 and 8.0 mg/kg).


RESULTS
The most commonly reported adverse event was headache, which was generally reported to be mild. The mean bioavailability of 3TC was 82% following oral administration. The majority of the dose (approximately 70%) was excreted unchanged in the urine.


CONCLUSIONS
Overall, 3TC was well tolerated following dosing, and there were no significant changes in the safety parameters measured. Phase I/II clinical trials with 3TC are ongoing to evaluate its safety, pharmacokinetics and preliminary activity.
van Leeuwen
R
R
Department of Internal Medicine (AIDS Unit), Academic Medical Centre, University of Amsterdam, The Netherlands.
Lange
J M
JM
Hussey
E K
EK
Donn
K H
KH
Hall
S T
ST
Harker
A J
AJ
Jonker
P
P
Danner
S A
SA
D000284:Administration, Oral; D000328:Adult; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004361:Drug Tolerance; D015658:HIV Infections / Q000188:drug therapy*; D006261:Headache / Q000139:chemically induced; D006801:Humans; D007262:Infusions, Intravenous; D019259:Lamivudine; D008297:Male; D008875:Middle Aged; D018894:Reverse Transcriptase Inhibitors; D016047:Zalcitabine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use
D018894:Reverse Transcriptase Inhibitors; D019259:Lamivudine; D016047:Zalcitabine