Study to Determine the Pharmacokinetic Behavior of Antiretroviral Drugs in Patients Infected by HIV

Germans Trias i Pujol Hospital675 enrolled

Overview

The purpose of this study is to characterise the pharmacokinetic profiles of non-nucleoside analog reverse transcriptase inhibitors (NNRTIs) and protease inhibitors (PIs), and the influence of the individual characteristics on the pharmacokinetic parameters in the Spanish population of HIV-infected subjects.

The antiretrovirals were administered conventionally according to fixed dosage systems, or depending on the weight of the individual in the case of certain agents. However, the plasma levels of antiretrovirals following the administration of a fixed dose present a marked interindividual variability. Moreover, a significant proportion of the patients on treatment with PIs presented plasma levels regarded as suboptimal in previous studies. Moreover, for the correct modification of the dosage of a drug, populational data on its pharmacokinetic behaviour during the dosing interval is required. Only by integrating this information with the specific characteristics of each individual is it possible, using mathematical models, to estimate the effect that a modification of the dosage of the drug would have on its plasma concentration. However, populational data on the pharmacokinetic behaviour of antiretroviral agents are still very limited at this moment, and have not always been obtained in populations similar to the one to which they are to be applied. Thus, knowing the pharmacokinetic behaviour of the antiretroviral agents in our population and the influence of certain individual characteristics on this behaviour may be of great interest, since only in this way will we be able to tailor the dosage of antiretrovirals reliably in our patients.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

675

Conditions

HIV Infections

Interventions

NevirapineDRUG

tablets 200 mg, 400 mg/day

EfavirenzDRUG

tablets 600 mg, 600 mg/day

Indinavir/ritonavirDRUG

Indinavir: capsules 400 mg, 1600 mg/day Ritonavir: capsules 100 mg, 200 mg/day

Nelfinavir

Eligibility

Sex: ALLMin age: 18 YearsMax age: 80 Years

Medical Language ↔ Plain English

Inclusion Criteria: 1. Age higher than 18 years. 2. Documented HIV infection (at least one positive Western-blot) 3. Stable antiretroviral treatment with PI or NNRTI, no changes over the last 4 weeks. 4. Women may not be of fertile age (defined as at least one year from menopause or undergoing any surgical sterilisation technique), or negative pregnancy test. Exclusion Criteria: 1. Subjects on treatment with more than one PI or with combinations of PI and NNRTI (the use of ritonavir in doses below 400 mg BID will not be regarded as a second PI). 2. Treatment with other drugs with known significant pharmacological interactions with the investigational drug over the previous two weeks. 3. Unsuitable adherence to treatment (one or more doses omitted in the last week, or two or more doses omitted in the last two weeks). 4. Presence of clinical findings or a background of gastrointestinal disease or digestive surgery that may interfere in the pharmacokinetics of the medication. 5. Active consumption of alcohol (\>50 grams/day) or illegal drugs (except cannabis). 6. In the case of women, pregnancy or breastfeeding. 7. Record or suspicion of inability to cooperate properly

Locations (6)

Germans Trias i Pujol Hospital

Badalona, Barcelona, Spain

Hospital de Figueres

Figueras, Barcelona, Spain

Fundació Hospital-Asil de Granollers

Granollers, Barcelona, Spain

Hospital de Vic

Vic, Barcelona, Spain

Outcomes

Primary Outcomes

The primary endpoint is the plasma concentration of the PI/NNRTI drugs (Ka absorption constant, CI: plasma clearance, Vd: volume of distribution).

Time frame: In the 12 hour (h) pharmacokinetic curve