OBJECTIVE: The influence of ritonavir-boosted darunavir coadministration on nevirapine pharmacokinetics was investigated in HIV-infected patients using a population-based approach. METHODS: The population was composed of 51 patients (89 samples; 42 patients treated with an antiretroviral regimen containing nevirapine and nucleoside/nucleotide reverse transcriptase inhibitors and nine patients treated with a regimen containing a combination of nevirapine and darunavir). A one-compartment model with first-order absorption was fitted to the data using nonmem version V (GloboMax, Ellicott City, MD, USA). RESULTS: Relationships were established between nevirapine clearance (Cl) and age (Cl/F=2.42+47.2/age, where F denotes bioavailability) and between nevirapine volume of distribution (V(d)) and the presence of darunavir in the antiretroviral regimen [V(d)/F=38.0+75.0 (1 - darunavir coadministration), where darunavir coadministration is 1 for patients treated with a combination of nevirapine and darunavir and 0 for other patients]. According to this final model, a significant decrease in the means of Cl/F (3.84 +/- 0.92 vs. 2.76 +/- 1.00 L/h; P<0.05) and V(d)/F (93.2 +/- 31.10 vs. 39.8 +/- 6.97 L; P<0.0001) and an increase in the mean of nevirapine trough plasma concentrations (3.68 +/- 1.69 vs. 5.35 +/- 3.20 mg/L; P<0.05) are observed if nevirapine is used in combination with darunavir. CONCLUSIONS: These results suggest that nevirapine exposure is increased when nevirapine is administered in combination with darunavir and that therapeutic drug monitoring of nevirapine should be performed if this antiretroviral regimen is considered.
OBJECTIVE: The influence of ritonavir-boosted darunavir coadministration on nevirapine pharmacokinetics was investigated in HIV-infectedpatients using a population-based approach. METHODS: The population was composed of 51 patients (89 samples; 42 patients treated with an antiretroviral regimen containing nevirapine and nucleoside/nucleotide reverse transcriptase inhibitors and nine patients treated with a regimen containing a combination of nevirapine and darunavir). A one-compartment model with first-order absorption was fitted to the data using nonmem version V (GloboMax, Ellicott City, MD, USA). RESULTS: Relationships were established between nevirapine clearance (Cl) and age (Cl/F=2.42+47.2/age, where F denotes bioavailability) and between nevirapine volume of distribution (V(d)) and the presence of darunavir in the antiretroviral regimen [V(d)/F=38.0+75.0 (1 - darunavir coadministration), where darunavir coadministration is 1 for patients treated with a combination of nevirapine and darunavir and 0 for other patients]. According to this final model, a significant decrease in the means of Cl/F (3.84 +/- 0.92 vs. 2.76 +/- 1.00 L/h; P<0.05) and V(d)/F (93.2 +/- 31.10 vs. 39.8 +/- 6.97 L; P<0.0001) and an increase in the mean of nevirapine trough plasma concentrations (3.68 +/- 1.69 vs. 5.35 +/- 3.20 mg/L; P<0.05) are observed if nevirapine is used in combination with darunavir. CONCLUSIONS: These results suggest that nevirapine exposure is increased when nevirapine is administered in combination with darunavir and that therapeutic drug monitoring of nevirapine should be performed if this antiretroviral regimen is considered.
Authors: Elin Svensson; Jan-Stefan van der Walt; Karen I Barnes; Karen Cohen; Tamara Kredo; Alwin Huitema; Jean B Nachega; Mats O Karlsson; Paolo Denti Journal: Br J Clin Pharmacol Date: 2012-09 Impact factor: 4.335
Authors: Betty J Dong; Yu Zheng; Michael D Hughes; Adam Frymoyer; Davide Verotta; Patricia Lizak; Frederick Sawe; Judith S Currier; Shahin Lockman; Francesca T Aweeka Journal: AIDS Date: 2012-04-24 Impact factor: 4.177
Authors: Mina Nikanjam; Desiré Kabamba; Tim R Cressey; David Burger; Francesca T Aweeka; Edward P Acosta; Stephen A Spector; Edmund V Capparelli Journal: Antimicrob Agents Chemother Date: 2012-08-06 Impact factor: 5.191