Pharmacokinetics of lamivudine & stavudine in generic fixed-dose combinations in HIV-1 infected adults in India.
OBJECTIVE
Antiretroviral drug concentrations are important determinants of clinical response to a drug accounting for both toxicity and efficacy. Several factors such as age, ethnicity, body weight and patients' immune status may influence antiretroviral drug concentrations. The aim of the study was to determine the influence of immunological status, sex and body mass index on the steady state pharmacokinetics of lamivudine (3TC) and stavudine (d4T) in HIV-infected adults, who were undergoing treatment with generic fixed dose combinations (FDC) of these drugs in India.


METHODS
Twenty seven HIV-1 infected patients receiving antiretroviral treatment (ART) for at least two weeks at the Government ART clinic at Tambaram, Chennai, took part in the study. Serial blood samples were collected predosing and at different time points after drug administration. Plasma 3TC and d4T levels were estimated by HPLC.


RESULTS
The patients' immune status, sex or body mass index had no impact on the pharmacokinetics of 3TC. In the case of d4T, peak concentration was significantly lower in patients with CD4 cell counts < 200 cells/microl than those with > or = 200 cells/ microl (P < 0.05), but were within the therapeutic range. The mean CD4 cell counts increased from 101 cells/microl at initiation of ART to 366 cells/microl at 12 months of treatment.


CONCLUSIONS
Blood levels of 3TC and d4T drugs that are part of generic FDCs commonly used by HIV-infected individuals in India were within the therapeutic range and not influenced by nutritional or immune status. There was a significant improvement in CD4 cell counts over 12 months of treatment. Indian generic FDCs manufactured and used widely in the developing world provide effective concentrations of antiretroviral drugs.
Hemanth Kumar
A K
AK
Department of Clinical Research, Tuberculosis Research Centre (ICMR), Chennai, India.
Ramachandran
Geetha
G
Rajasekaran
S
S
Padmapriyadarsini
C
C
Narendran
G
G
Anitha
S
S
Subramanyam
Sudha
S
Kumaraswami
V
V
Swaminathan
Soumya
S
D000328:Adult; D019380:Anti-HIV Agents / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use; D004338:Drug Combinations; D005260:Female; D015658:HIV Infections / Q000097:blood / Q000188:drug therapy*; D015497:HIV-1; D006801:Humans; D007194:India; D019259:Lamivudine / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D011247:Pregnancy; D018119:Stavudine / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use
D019380:Anti-HIV Agents; D004338:Drug Combinations; D019259:Lamivudine; D018119:Stavudine