HIV Infections
Conditions
Keywords
protease inhibitors, non-nucleoside analog reverse transcriptase inhibitors, pharmacokinetic models, treatment experienced, HIV
Brief summary
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.
Detailed description
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.
Interventions
DRUGNevirapine
tablets 200 mg, 400 mg/day
DRUGEfavirenz
tablets 600 mg, 600 mg/day
Indinavir: capsules 400 mg, 1600 mg/day Ritonavir: capsules 100 mg, 200 mg/day
DRUGNelfinavir
tablets 250 mg, 2500 mg/day
Saquinavir: tablets 500 mg, 2000 mg/day Ritonavir: tablets 100 mg, 200 mg/day
DRUGLopinavir/ritonavir
tablets lopinavir 200 mg + ritonavir 50 mg, 800/200 mg/day
DRUGAtazanavir
capsules 200 mg, 400 mg/day
Atazanavir: capsules 150 mg, 300 mg/day Ritonavir: capsules 100 mg, 200 mg/day
DRUGFos-amprenavir/ritonavir
Fos-amprenavir: capsules 700 mg, 1400 mg/day Ritonavir: capsules 100 mg, 200 mg/day
DRUGTipranavir/ ritonavir
Tipranavir: tablets 250 mg, 1000 mg/day Ritonavir: capsules 100 mg, 400 mg/day
Darunavir: tablets 300 mg, 1200 mg/day Ritonavir: capsules 100 mg, 200 mg/day
Sponsors
Fundación FLS de Lucha Contra el Sida, las Enfermedades Infecciosas y la Promoción de la Salud y la Ciencia
Germans Trias i Pujol Hospital
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The primary endpoint is the plasma concentration of the PI/NNRTI drugs (Ka absorption constant, CI: plasma clearance, Vd: volume of distribution). | In the 12 hour (h) pharmacokinetic curve |
Secondary
| Measure | Time frame |
|---|---|
| Clinical: weight, height, liver/renal impairment, HIV infection stage, tobacco/alcohol consumption | In the 12 h pharmacokinetic curve |
| Adverse events | In the 12 h pharmacokinetic curve |
| Laboratory: creatinine, albumin, Quick Index, bilirubin, GOT, GPT, GGT, FA, CD4 lymphocyte count, HIV viral load, HBsAg and anti-HCV, alpha acid glycoprotein | In the 12 h pharmacokinetic curve |
| Demographic: race, gender, age | In the 12 h pharmacokinetic curve |
| Pharmacokinetics: maximum concentration (Cmax), time to maximum concentration (Tmax), plasma concentration at the end of the posology interval (Ctrough), half-life (T1/2), area under the curve (ABC) | In the 12 h pharmacokinetic curve |
| Genetic study of polymorphism of CYP3A4 and P-glycoprotein | In the 12 h pharmacokinetic curve |
| Antiretroviral and concomitant treatment, adherence (number of doses omitted in the last two weeks) | In the 12 h pharmacokinetic curve |
Countries
Spain
Outcome results
None listed