Pharmacokinetics of saquinavir hard gel/ritonavir (1000/100 mg twice daily) when administered with tenofovir diproxil fumarate in HIV-1-infected subjects.

AIMS To investigate whether the administration of tenofovir diproxil fumarate 300 mg once daily alters the plasma pharmacokinetics of the saquinavir hard gel/ritonavir combination in HIV-1 infected individuals. METHODS On day 1, 12 h pharmacokinetic profiles for saquinavir/ritonavir (1000/100 mg given twice daily) were obtained for 18 subjects. All subjects were receiving ongoing treatment with a saquinavir/ritonavir-containing regimen. Tenofovir diproxil fumarate 300 mg given once daily was then added to the regimen and blood sampling was repeated at days 3 and 14. Saquinavir and ritonavir concentrations were measured by HPLC-MS/MS, and tenofovir concentrations by HPLC with UV detection. RESULTS Following the addition of tenofovir diproxil fumarate to the regimen, saquinavir and ritonavir plasma concentrations were not significantly different compared with day 1. Thus the geometric mean ratios (95% confidence intervals) for the area under the concentration-time curve were 1.16 (0.97, 1.59) and 0.99 (0.87, 1.30) for saquinavir and 1.05 (0.92, 1.28) and 1.08 (0.97, 1.30) for ritonavir, on days 3 and 14, respectively. CONCLUSIONS Tenofovir diproxil fumarate did not alter the pharmacokinetics of saquinavir hard gel/ritonavir.

[1]  S. Khoo,et al.  Intra-individual variability in lopinavir plasma trough concentrations supports therapeutic drug monitoring. , 2003, AIDS.

[2]  D. Droz,et al.  Tenofovir-related nephrotoxicity in human immunodeficiency virus-infected patients: three cases of renal failure, Fanconi syndrome, and nephrogenic diabetes insipidus. , 2003, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[3]  S. Chou,et al.  Fatal lactic acidosis and acute renal failure after addition of tenofovir to an antiretroviral regimen containing didanosine. , 2003, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[4]  M. Kazatchkine,et al.  Renal lesions in HIV-1-positive patient treated with tenofovir. , 2003, AIDS.

[5]  T. Antoniou,et al.  Tenofovir: A Nucleotide Analog for The Management of Human Immunodeficiency Virus Infection , 2003, Pharmacotherapy.

[6]  M. Perazella,et al.  Rapid communication: acute renal failure associated with tenofovir: evidence of drug-induced nephrotoxicity. , 2002, The American journal of the medical sciences.

[7]  J. Rossert,et al.  Fanconi syndrome and renal failure induced by tenofovir: a first case report. , 2002, American journal of kidney diseases : the official journal of the National Kidney Foundation.

[8]  R. Haubrich,et al.  Therapeutic drug monitoring in HIV infection: current status and future directions , 2002, AIDS.

[9]  S. Piscitelli,et al.  Interactions among drugs for HIV and opportunistic infections. , 2001, The New England journal of medicine.

[10]  J. Drewe,et al.  Interactions of HIV protease inhibitors with ATP-dependent drug export proteins. , 1999, Molecular pharmacology.

[11]  K. Cundy.  Clinical Pharmacokinetics of the Antiviral Nucleotide Analogues Cidofovir and Adefovir , 1999, Clinical pharmacokinetics.