[Tenofovir: pharmacology and interactions].
Tenofovir is a nucleotide analogue and consequently its mechanism of action differs from that of nucleoside analogues. This drug is administered orally in the form of disoproxil ester, which is deesterified to achieve a bioavailability of more than 20%. This bioavailability slightly increases if tenofovir is taken with a fat-rich meal. This drug has broad tissue distribution, aided by its small molecular size and very low protein binding, and is eliminated as unchanged drug in the urine through glomerular filtration and active tubular secretion. Because of this latter characteristic, dosage adjustments are required in patients with renal insufficiency. The intracellular half-life of tenofovir is more than 10 times greater than the plasma half-life. Because of the pharmacokinetic profile of tenofovir, interactions with other drugs are scarce. Within the class of antiretroviral agents, an increase in the bioavailability of didanosine has been described, leading to the recommendation that the dose of didanosine be reduced when used in combination with tenofovir. Tenofovir can be used without adjustments with other nucleoside and nonnucleoside reverse transcriptase inhibitors. Equally, tenofovir seems to have no effect on the pharmacokinetics of protease inhibitors although these latter agents may produce a slight increase in the bioavailability of tenofovir, which seems to be of little clinical relevance. The absence of interactions with other non-antiretroviral agents has been reported.
Azanza
José Ramón
JR
Servicio de Farmacología Clínica, Clínica Universitaria de Navarra, Facultad de Medicina. Universidad de Navarra, Pamplona, España. jrazanza@unav.es
García Quetglas
Emilio
E
Sádaba
Belén
B
Gómez-Giu
Almudena
A
D000225:Adenine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use; D000293:Adolescent; D000328:Adult; D000368:Aged; D019380:Anti-HIV Agents / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D001682:Biological Availability; D001711:Biotransformation; D002648:Child; D002675:Child, Preschool; D004279:DNA, Viral / Q000096:biosynthesis; D003838:Deoxyadenine Nucleotides / Q000037:antagonists & inhibitors; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D006678:HIV / Q000187:drug effects / Q000502:physiology; D015658:HIV Infections / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism; D017320:HIV Protease Inhibitors / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D007674:Kidney Diseases / Q000150:complications / Q000378:metabolism; D008107:Liver Diseases / Q000150:complications / Q000378:metabolism; D008875:Middle Aged; D015394:Molecular Structure; D063065:Organophosphonates / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D018894:Reverse Transcriptase Inhibitors / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D000068698:Tenofovir; D014779:Virus Replication / Q000187:drug effects; D055815:Young Adult
D019380:Anti-HIV Agents; D004279:DNA, Viral; D003838:Deoxyadenine Nucleotides; D017320:HIV Protease Inhibitors; D063065:Organophosphonates; D018894:Reverse Transcriptase Inhibitors; C025435:deoxyadenosine-5'-tri-3'-diphosphate; D000068698:Tenofovir; D000225:Adenine