A study of the pharmacokinetic interaction between lamivudine and alpha interferon.
OBJECTIVE
This study was designed to investigate any possible pharmacokinetic interaction between lamivudine and alpha interferon as potential candidates for combination therapy for the treatment of hepatitis B virus (HBV).


METHODS
Nineteen healthy male, Caucasian volunteers, aged 20-41 years and weighing 60.5-83.5 kg completed this open, non-randomised study. They each received a single, abdominal, deep s.c. injection of 10 mIU alpha interferon on day 1, followed by a wash-out period of at least 1 week. Subjects then began a 7-day course of lamivudine (100 mg) followed by a further 10-mIU alpha-interferon injection directly after oral lamivudine dosing. Blood and urine samples were taken pre- and post-dose for alpha-interferon and/or lamivudine assay.


RESULTS
Lamivudine was safe and well tolerated in all subjects. No adverse events were reported in subjects on lamivudine, whereas 106 adverse events considered attributable to alpha interferon were recorded. Statistical analysis of pharmacokinetic parameters indicated no significant effect of lamivudine on alpha-interferon pharmacokinetics. There was a small statistically significant reduction (approximately 10%) in the area under the lamivudine concentration time curve on co-administration with alpha interferon and a concomitant increase in clearance, which is not considered clinically relevant.


CONCLUSIONS
Alpha interferon and lamivudine can be co-administered with no requirement for dose modification, as there was no clinically significant difference in the pharmacokinetics of either drug.
Johnson
M A
MA
Department of Clinical Pharmacology, Glaxo Wellcome Incorporated, Research Triangle Park, North Carolina 27709, USA. MAJ4852@glaxowellcome.com
Jenkins
J M
JM
Bye
C
C
D000328:Adult; D019380:Anti-HIV Agents / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D000998:Antiviral Agents / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D019540:Area Under Curve; D004338:Drug Combinations; D006207:Half-Life; D006509:Hepatitis B / Q000188:drug therapy; D006801:Humans; D016898:Interferon-alpha / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D019259:Lamivudine / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D008297:Male; D008657:Metabolic Clearance Rate
D019380:Anti-HIV Agents; D000998:Antiviral Agents; D004338:Drug Combinations; D016898:Interferon-alpha; D019259:Lamivudine