The clinical pharmacology of antiretrovirals in development.
Drugs in development for the management of HIV type 1 (HIV-1) infection include agents in existing classes and agents of novel classes. Of existing classes, new protease inhibitors, nucleoside reverse transcriptase inhibitors and non-nucleoside reverse transcriptase inhibitors are in development. Novel therapeutic approaches include the development of chemokine receptor (CCR)5 antagonists, integrase inhibitors and maturation inhibitors. CCR5 antagonists are thought to inhibit HIV-1 entry into host cells by occupying a specific site on the CCR5 receptor, preventing attachment of the HIV-1 envelope protein gp120. Integrase inhibitors are small synthetically prepared molecules that block RNA/DNA interactions and modify protein or enzyme synthesis. Data on the pharmacokinetics and pharmacodynamics of these new antiretroviral agents continue to generate interest. This review reports the known data on the pharmacokinetics of experimental antiretrovirals, and describe the main drug-drug interactions studied so far.
Winston
Alan
A
Imperial College, Clinical Trials Unit, Ground Flood, Winston Churchill Wing, St. Mary's Hospital, Praed Street, London W2 1NY, UK. awinston@imperial.ac.uk
Mallon
Patrick Wg
PW
Boffito
Marta
M
D000818:Animals; D044966:Anti-Retroviral Agents / Q000493:pharmacokinetics* / Q000494:pharmacology / Q000627:therapeutic use; D065100:CCR5 Receptor Antagonists; D002986:Clinical Trials as Topic; D003510:Cyclohexanes / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use; D000069454:Darunavir; D004353:Drug Evaluation, Preclinical; D004347:Drug Interactions; D015658:HIV Infections / Q000188:drug therapy* / Q000201:enzymology; D019428:HIV Integrase Inhibitors / Q000493:pharmacokinetics / Q000627:therapeutic use; D017320:HIV Protease Inhibitors / Q000493:pharmacokinetics / Q000627:therapeutic use; D015497:HIV-1 / Q000187:drug effects* / Q000201:enzymology; D006801:Humans; D000077592:Maraviroc; D009570:Nitriles; D009930:Organic Chemicals / Q000493:pharmacokinetics / Q000627:therapeutic use; D011480:Protease Inhibitors / Q000493:pharmacokinetics / Q000627:therapeutic use; D011724:Pyridazines / Q000493:pharmacokinetics / Q000627:therapeutic use; D011743:Pyrimidines; D011760:Pyrrolidinones; D000068898:Raltegravir Potassium; D019713:Receptors, CCR5 / Q000378:metabolism; D018894:Reverse Transcriptase Inhibitors / Q000493:pharmacokinetics / Q000627:therapeutic use; D013449:Sulfonamides / Q000493:pharmacokinetics / Q000627:therapeutic use; D014230:Triazoles / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use
D044966:Anti-Retroviral Agents; D065100:CCR5 Receptor Antagonists; D003510:Cyclohexanes; D019428:HIV Integrase Inhibitors; D017320:HIV Protease Inhibitors; D009570:Nitriles; D009930:Organic Chemicals; D011480:Protease Inhibitors; D011724:Pyridazines; D011743:Pyrimidines; D011760:Pyrrolidinones; D019713:Receptors, CCR5; D018894:Reverse Transcriptase Inhibitors; D013449:Sulfonamides; D014230:Triazoles; C451734:etravirine; D000068898:Raltegravir Potassium; D000077592:Maraviroc; D000069454:Darunavir