Cross-sectional Study for the Characterisation of the Pharmacokinetic Parameters of Protease Inhibitors and Non-nucleoside Analog Reverse Transcriptase Inhibitors in the Spanish Population of HIV-infected Subjects
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 675
- 试验地点
- 6
- 主要终点
- The primary endpoint is the plasma concentration of the PI/NNRTI drugs (Ka absorption constant, CI: plasma clearance, Vd: volume of distribution).
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age higher than 18 years.
- •Documented HIV infection (at least one positive Western-blot)
- •Stable antiretroviral treatment with PI or NNRTI, no changes over the last 4 weeks.
- •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.
排除标准
- •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).
- •Treatment with other drugs with known significant pharmacological interactions with the investigational drug over the previous two weeks.
- •Unsuitable adherence to treatment (one or more doses omitted in the last week, or two or more doses omitted in the last two weeks).
- •Presence of clinical findings or a background of gastrointestinal disease or digestive surgery that may interfere in the pharmacokinetics of the medication.
- •Active consumption of alcohol (>50 grams/day) or illegal drugs (except cannabis).
- •In the case of women, pregnancy or breastfeeding.
- •Record or suspicion of inability to cooperate properly
研究组 & 干预措施
NVP
Nevirapine
干预措施: Nevirapine (Drug)
EFV
Efavirenz
干预措施: Efavirenz (Drug)
INV
Indinavir/ritonavir
干预措施: Indinavir/ritonavir (Drug)
NFV
Nelfinavir
干预措施: Nelfinavir (Drug)
SQV
Saquinavir/ritonavir
干预措施: Saquinavir/ritonavir (Drug)
LPV
Lopinavir/ritonavir
干预措施: Lopinavir/ritonavir (Drug)
ATV
Atazanavir
干预措施: Atazanavir (Drug)
ATV/rtv
Atazanavir/ritonavir
干预措施: Atazanavir/ritonavir (Drug)
Fos-APV
Fos-amprenavir/ritonavir
干预措施: Fos-amprenavir/ritonavir (Drug)
TPV
Tipranavir/ritonavir
干预措施: Tipranavir/ ritonavir (Drug)
DRV
Darunavir/ritonavir
干预措施: Darunavir/ritonavir (Drug)
结局指标
主要结局
The primary endpoint is the plasma concentration of the PI/NNRTI drugs (Ka absorption constant, CI: plasma clearance, Vd: volume of distribution).
时间窗: In the 12 hour (h) pharmacokinetic curve
次要结局
- Demographic: race, gender, age(In the 12 h pharmacokinetic curve)
- Adverse events(In the 12 h pharmacokinetic curve)
- Clinical: weight, height, liver/renal impairment, HIV infection stage, tobacco/alcohol consumption(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)
- Antiretroviral and concomitant treatment, adherence (number of doses omitted in the last two weeks)(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)