In Silico Pharmacokinetics Evaluation of Forgiveness for Doravirine and Rilpivirine.
Ther Drug Monit
; 46(3): 391-396, 2024 Jun 01.
Article
en En
| MEDLINE
| ID: mdl-38158596
ABSTRACT
BACKGROUND:
This study aimed to evaluate the concentrations of rilpivirine (RLP) and doravirine (DOR) after 3 days-off using simulations from population pharmacokinetics models.METHODS:
The authors conducted a series of 500 sets of 10,000 Monte Carlo simulations to examine the steady-state conditions for 2 common dosage levels 25 mg/d for RLP and 100 mg/d for DOR. These simulations were conducted under 2 scenarios 1 without drug cessation and another after a 3-day break. The validity of the implementation was established through a comparison of median trough concentrations (C24h) with previously reported data. Subsequently, the proportion of simulated patients with C24h and C72h after 3 days-off (C72h/3do) that exceeded the inhibitory concentration 50 (IC50), 5.2 mcg/L for DOR and 20.5 mcg/L for RLP respectively, was calculated. The inhibitory quotient (IQ) was also computed, which was 6 times IC50 for DOR and 4.5 times IC50 for RLP. Finally, nomograms were constructed to estimate the probability of having C72h/3do > IC50 or > IQ for different ranges of C24h.RESULTS:
Simulated C24h median ± SD for RLP were 61.8 ± 0.4 mcg/L and for DOR 397 ± 0 mcg/L. For RLP, 99.3 ± 0.1% exceeded IC50 at C24h, 16.4 ± 0.4% at C72h/3do, and none surpassed the IQ threshold. In contrast, DOR had 100% ± 0% above IC50 at C24h, 93.6 ± 0.2% at C72h/3do, and 58.6 ± 0.5% exceeded the IQ.CONCLUSIONS:
These findings suggest that treatment with DOR may offer a more forgiving therapeutic profile than RLP, given the larger proportion of patients achieving effective drug exposure with DOR. However, it is important to acknowledge a significant limitation of this study, namely, the assumption that drug concentration is a perfect surrogate for drug effectiveness.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Piridonas
/
Triazoles
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Simulación por Computador
/
Método de Montecarlo
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Fármacos Anti-VIH
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Rilpivirina
Límite:
Humans
Idioma:
En
Revista:
Ther Drug Monit
Año:
2024
Tipo del documento:
Article
País de afiliación:
Francia