Population pharmacokinetics and dosing regimen optimisation of lopinavir in Chinese adults infected with HIV

Abstract

Lopinavir (LPV) is a protease inhibitor (PI) for the treatment of human immunodeficiency virus (HIV) infections. Current studies on LPV are mainly focused onCaucasians, and none have investigated the population pharmacokinetics (PPK) of LPV in Chinese population. The present study aimed to develop a PPK model for oral LPV in Chinese adults who are HIV-infected. A total of 460 LPV concentrations from 174 Chinese patients who received LPV/ritonavir (LPV/r) 400/ 100 mg orally every 12 hours (q12h) were analysed using the non-linear mixedeffects modelling approach. Simulations of the LPV concentration profile were performed with different dosing regimens. A one-compartment model with firstorder absorption and elimination process described the data. The estimated apparent clearance (CL/F) and volume of distribution (V/F) (% relative standard error [RSE]) for oral LPV were 5.9 L/h (3%) and 117 L (8%), respectively. Bodyweight was identified as a covariate on CL/F. In patients who weighed between 45 and 115 kg and received the standard 400/100 mg q12h regimen, the probability of achieving target trough concentration (C trough ) of 1 mg/L was >98% for PInaïve patients and the probability of achieving target C trough of 4 mg/L was <80% for PI-pretreated patients. This is the first population pharmacokinetic study to characterise the PK of LPV in Chinese patients with HIV infection. There were no obvious ethnic differences in the PK of LPV between the Chinese population and Caucasian population. The simulations demonstrated that the standard dosing regimen of 400/100 mg q12h (LPV/r tablets) appears to be sufficient for PI-naïve patients but suboptimal for PI-pretreated patients. Therefore, the regimen of 800/ 200 mg q12h was recommended for PI-pretreated patients. Further investigation of dosage recommendation could be helpful in optimising LPV therapy for HIV infections. K E Y W O R D SChinese patients, HIV, lopinavir, population pharmacokinetics, ritonavir, simulation Niu and Sun contributed equally to this work.

Therapy with lopinavir/ritonavir and hydroxychloroquine is associated with acute kidney injury in COVID-19 patients

“…Acute kidney injury (AKI) is a frequent complication in about 5% of hospitalized patients with coronavirus disease-2019 (COVID- 19) and an independent risk factor for in-hospital death [1]. 43.9% of COVID-19 patients exhibit proteinuria and 26.7% hematuria, which are both independent risk factors for mortality [1].…”

“…Hydroxychloroquine is N-dealkylated by CYP3A4 to the biologically active metabolite desethylhydroxychloroquine and the inactive metabolites desethylchloroquine and bidesethylchloroquine [14,15]. The oral bioavailability of lopinavir is low due to its rapid metabolism mainly by CYP3A4 and it is therefore co-administered with the CYP3A4 inhibitor ritonavir [16][17][18][19][20].…”

Optimization of Initial Dose Regimen for Sirolimus in Pediatric Patients With Lymphangioma

“…For example, in Wang et al's study, only body weight was fixed in the covariate model (Wang et al, 2020). And in other drug studies, such as in Niu et al's study, population pharmacokinetics and dosing regimen optimisation of lopinavir in Chinese adults infected with HIV, only body weight was included into model (Niu et al, 2019). However, due to the low incidence of lymphangioma, the present study has objective difficulties in the collection of children patients, resulting in the limited number of pediatric patients with lymphangioma.…”

“…For example, in Wang et al ’s study, only body weight was fixed in the covariate model ( Wang et al, 2020 ). And in other drug studies, such as in Niu et al ’s study, population pharmacokinetics and dosing regimen optimisation of lopinavir in Chinese adults infected with HIV, only body weight was included into model ( Niu et al, 2019 ).…”

Initial Dosage Recommendation for Sirolimus in Children With Tuberous Sclerosis Complex

“…Fortunately, the combination of population pharmacokinetics and Monte Carlo simulation can successfully predict and recommend the best initial dosing regimen, the method has been widely used in clinical practice (Niu et al, 2019;Ren et al, 2019;Tang et al, 2019;Wang et al, 2019b). For example, Ren et al (2019) reported population pharmacokinetics of voriconazole and optimization of dosage regimens based on Monte Carlo simulation in patients with liver cirrhosis, Niu et al (2019) reported that population pharmacokinetics and dosing regimen optimization of lopinavir in Chinese adults infected with HIV, Wang et al (2019b) reported population pharmacokinetics and initial dosing regimen optimization of cyclosporin in pediatric hemophagocytic lymphohistiocytosis patients, Tang et al (2019) reported population pharmacokinetics and dosing optimization of amoxicillin in neonates and young infants. Based on these studies, the present study was to establish a population Partial concentration values were collected in a previous study (Wang et al, 2018).…”