Clinically relevant enantiomer specific R- and S-praziquantel pharmacokinetic drug-drug interactions with efavirenz and ritonavir.
Pharmacol Res Perspect
; 9(3): e00769, 2021 05.
Article
em En
| MEDLINE
| ID: mdl-33929078
ABSTRACT
We conducted a clinical study to determine the effect of efavirenz and ritonavir on the pharmacokinetics of R- and S-PZQ in healthy male participants. This was toward evaluating the risk of drug-drug interactions, which may occur after PZQ administration to HIV patients on efavirenz or ritonavir containing regimens. A non-randomized, open-label, single-dose, one sequence crossover study with 2 arms was conducted. We gave 26 healthy volunteers a single oral dose of 40 mg/kg PZQ followed by a daily oral dose of either 400 mg efavirenz or 100 mg ritonavir for 14 consecutive days. On day 14, they ingested a single 40 mg/kg dose of PZQ. We measured plasma levels up to 12 h on day 1 and day 14. Samples were analyzed by LC-MS. Pharmacokinetic analysis was conducted in WinNonlin to determine the primary endpoints (plasma T1/2 , Cmin , and AUC). Efavirenz had a significant effect on the pharmacokinetics of PZQ (p < .05), reducing the AUC by 4-fold (1213.15 vs. 281.35 h·ng/ml for R-PZQ and 5669 vs. 871.84 h·ng/ml for S-PZQ). Ritonavir had no significant effect on R-PZQ but increased the AUC 2-fold for S-PZQ (p < .05) (4154.79 vs. 7291.05 h·ng/ml). Using PZQ in HIV patients needs investigation, as there is a risk of both treatment failure and adverse effects because of induction and inhibition, respectively.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Praziquantel
/
Ritonavir
/
Fármacos Anti-HIV
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Ciclopropanos
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Benzoxazinas
/
Alcinos
/
Anti-Helmínticos
Tipo de estudo:
Clinical_trials
Limite:
Adult
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Humans
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Male
Idioma:
En
Revista:
Pharmacol Res Perspect
Ano de publicação:
2021
Tipo de documento:
Article