Tenofovir: farmacología e interacciones / Tenofovir: pharmacology and interactions

Tenofovir es un análogo de los nucleótidos y, por ello, presenta un mecanismo de acción diferente al de los análogos a los nucleósidos. Se administra por vía oral en forma de éster disoproxil, que es desesterificado para alcanzar una biodisponibilidad, que supera el 20%, y que aumenta ligeramente si el fármaco se ingiere con grasas. Presenta una distribución tisular amplia, facilitada por el pequeño tamaño de la molécula y su escasa fijación a proteínas, y se elimina en su práctica totalidad en forma activa por la orina, a través de filtración glomerular y secreción tubular activa. Esta circunstancia obliga a realizar un ajuste de la dosis cuando hay insuficiencia renal. De forma característica, presenta una semivida intracelular que supera en más de 10 veces a la plasmática. Su perfil farmacocinético le configura como un fármaco con poco potencial de producir o de presentar interacciones con otros fármacos. Así, dentro de los antirretrovirales se ha descrito un aumento de la biodisponibilidad de didanosina que conlleva la recomendación de utilizarlo en dosis inferior a la habitual, mientras que puede utilizarse sin ajustes con otros inhibidores análogos y no análogos. Tampoco parece alterar la farmacocinética de los fármacos inhibidores de la proteasa, aunque éstos pueden producir un aumento ligero de la biodisponibilidad de tenofovir que parece tener escasa trascendencia clínica. Se ha señalado la ausencia de interacciones con otros fármacos no antirretrovirales(AU)

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(AU)

Tenofovir: farmacología e interacciones / Tenofovir: pharmacology and interactions

Tenofovir es un análogo de los nucleótidos y, por ello, presenta un mecanismo de acción diferente al de los análogos a los nucleósidos. Se administra por vía oral en forma de éster disoproxil, que es desesterificado para alcanzar una biodisponibilidad, que supera el 20%, y que aumenta ligeramente si el fármaco se ingiere con grasas. Presenta una distribución tisular amplia, facilitada por el pequeño tamaño de la molécula y su escasa fijación a proteínas, y se elimina en su práctica totalidad en forma activa por la orina, a través de filtración glomerular y secreción tubular activa. Esta circunstancia obliga a realizar un ajuste de la dosis cuando hay insuficiencia renal. De forma característica, presenta una semivida intracelular que supera en más de 10 veces a la plasmática. Su perfil farmacocinético le configura como un fármaco con poco potencial de producir o de presentar interacciones con otros fármacos. Así, dentro de los antirretrovirales se ha descrito un aumento de la biodisponibilidad de didanosina que conlleva la recomendación de utilizarlo en dosis inferior a la habitual, mientras que puede utilizarse sin ajustes con otros inhibidores análogos y no análogos. Tampoco parece alterar la farmacocinética de los fármacos inhibidores de la proteasa, aunque éstos pueden producir un aumento ligero de la biodisponibilidad de tenofovir que parece tener escasa trascendencia clínica. Se ha señalado la ausencia de interacciones con otros fármacos no antirretrovirales

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

[Tenofovir: pharmacology and interactions]. / Tenofovir: farmacología e interacciones.

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.