JAC Advance Access originally published online on September 5, 2005
Journal of Antimicrobial Chemotherapy 2005 56(4):790-792; doi:10.1093/jac/dki314
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Higher plasma lopinavir concentrations are associated with a moderate rise in cholestasis markers in HIV-infected patients
1 Infectious Disease Department, San Raffaele Scientific Institute, Via Stamira d'Ancona 20, 20122 Milan, Italy; 2 Laboraf, San Raffaele Scientific Institute, Via Olgettina 60, 20122 Milan, Italy
Received 24 March 2005; returned 27 April 2005; revised 26 July 2005; accepted 9 August 2005
* Corresponding author. Tel: +39-02-26437934; Fax: +39-02-26437903; E-mail: elena.seminari{at}hsr.it
Objectives: The aim of this study was to evaluate the correlation between liver function markers (necrosis and cholestasis) and plasma lopinavir levels in a cohort of HIV-infected patients treated with lopinavir and ritonavir.
Patients and methods: The blood samples for determining steady-state Ctrough lopinavir levels and analysing liver function were drawn from fasting patients. Steady-state Ctrough lopinavir levels, liver function and immuno-virological markers were assessed on the same day. Plasma lopinavir and ritonavir levels were determined by means of high-performance liquid chromatography.
Results: One hundred and forty-nine patients were included in the analysis [57 were HCV co-infected (34%) and 10 were HBV co-infected (6.7%)]; they had been treated with lopinavir/ritonavir for a median of 232 days (range 132–282). All patients received lopinavir/ritonavir [400/100 mg twice daily or 533/133 mg twice daily if amprenavir or a non-nucleoside reverse transcriptase inhibitor (NNRTI) was part of therapy] and concomitant therapy with NRTI(s). Median (interquartile) lopinavir trough levels were 6391 ng/mL (4121–8726), 5662 (3585–8893) and 6819 ng/mL (5324–8726) in the patients with HIV alone and those with HIV/HCV (or HBV) co-infection, respectively (P = not significant). Univariate analysis showed a significant association between the cholestasis markers and Ctrough lopinavir level. Multivariate analysis selected only gamma glutamyltranspeptidase (GGT) (OR = 1.010, 95% CI: 1.002–1.021) as being independently associated with plasma lopinavir levels of >6425 ng/mL; alkaline phosphatase (OR = 1.004, 95% CI: 1.000–1.010; P = 0.08) and total bilirubin (OR = 3.118, 95% CI: 0.980–11.715; P = 0.07) were not associated.
Conclusions: Elevated lopinavir concentrations are associated with raised GGT.
Keywords: pharmacokinetics , drug monitoring , HIV antiviral pharmacology
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