Drug-drug interaction between rifabutin and dolutegravir: A population pharmacokinetic model.

Aida N Kawuma, Roeland E Wasmann, Kelly E Dooley, Gary Maartens, Paolo Denti

British journal of clinical pharmacology 2023 Mar

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Rifampicin, a potent enzyme inducer, causes marked reduction of dolutegravir exposure. Rifabutin, a less potent enzyme inducer, may offer an alternative to rifampicin. We aimed to characterize the population pharmacokinetics of dolutegravir when co-administered with rifabutin. We extended an existing dolutegravir model to include data from volunteers co-administered with dolutegravir 50 mg and rifabutin 300 mg once daily. We ran simulations of dolutegravir with and without rifabutin co-administration and compare dolutegravir trough concentrations with the IC90 and EC90 of 0.064 and 0.3 mg/L, respectively. Rifabutin decreased dolutegravir's volume of distribution by 33.1% (95% confidence interval 25.1%-42.3%) but did not affect the area under the concentration-time curve. Simulations showed that when 50 mg dolutegravir is co-administered with rifabutin once daily, the probability to attain trough concentrations above the IC90 of 0.064 mg/L is more than 99%. Therefore, there is no need for dolutegravir dose adjustment. Rifabutin may offer an alternative to rifampicin for the treatment of HIV/tuberculosis co-infected individuals. © 2022 The Authors. British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.

Citation

Aida N Kawuma, Roeland E Wasmann, Kelly E Dooley, Gary Maartens, Paolo Denti. Drug-drug interaction between rifabutin and dolutegravir: A population pharmacokinetic model. British journal of clinical pharmacology. 2023 Mar;89(3):1216-1221