Individualization of Dosage Regimens in Obese Patients: Application to Acyclovir
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 20
- 试验地点
- 1
- 主要终点
- Renal elimination clearance
研究概览
简要总结
The number of obese people will reach 50% of the world population by 2035. Obesity is a chronic disease. For obese patients, dosage regimens have been determined for patients with a "normal" BMI between 20-30 kg/m2. Based on plasma and urine concentrations, a pharmacokinetic model will be performed to study in healthy volunteers, the predictive character of lean mass, measured by DEXA, on renal elimination and therefore on acyclovir exposure. The main objective of this study is to evaluate, in 4 volunteers groups representative of (1) non-obese (18-24.9 kg/m2), (2) overweight (25-29.9 kg/m2), (3) grade 1 obesity (30-34.9 kg/m2) and (4) grade 2 obesity (35-39.9 kg/m2), the predictive nature of lean mass, measured by DEXA, on renal elimination and therefore on acyclovir exposure.
详细描述
This study will complement the clinical data on acyclovir in healthy volunteers considering that current knowledge in terms of drugs use in obese subjects is not sufficient to guarantee the efficacy and/or toxicity absence of exposure. As a consequence, this lack of certainties leads physicians to propose dosages without exceeding a threshold defined according to (i) their experience, (ii) data obtained for BMI < 30 kg/m2 and/or (iii) an approximate criterion derived from the total weight (adjusted weight...). Acyclovir is a systemic antiviral drug indicated for the treatment of Herpes Simplex virus (HSV) and Varicella Zoster (VZV) mucosal infections at 15 mg/kg/d in three divided doses, or more severe infections (e.g., herpetic meningoencephalitis) at higher dosage regimen (30 to 45 mg/kg/d in three divided doses).
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 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 50 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •healthy volunteers with a BMI between 18 and 39,9 kg/m2, divided into 4 groups: 5 non-obese volunteers (BMI between 18 and 24,9 kg/m2), 5 overweight volunteers (BMI between 25 and 29,9 kg/m2), 5 volunteers with grade 1 obesity (BMI between 30 and 34,9 kg/m2) and 5 volunteers with grade 2 obesity (BMI between 35 and 39,9 kg/m2),
- •volunteers with a aGFR > 50 ml/min,
- •with a good venous pathway for kinetics,
- •women on contraception or postmenopausal women,
- •person who has given written consent and affiliated with the public health insurance.
排除标准
- •volunteers with nephrotoxic co-prescriptions and/or co-prescriptions that would modify the pharmacokinetics of acyclovir like diuretics, NSAIDs or statins,
- •having presented serious allergies to a drug (e.g. angioedema...), with large parenchyma insufficiencies (e.g., hepatic insufficiency, heart failure...),
- •with diabetes or taking anti-diabetics due to the possible deterioration of renal function in diabetic patients,
- •with arterial hypertension or taking antihypertensive drugs due to the possible modification of renal clearance by modification of blood flow,
- •drug interactions with acyclovir (H2 receptor antagonists (e.g., Cimetidine), Probenecid, Mycophenolate Mofetil, Lithium, Anti-calcineurins (Ciclosporin, Tacrolimus)),
- •volunteers taking anticoagulants,
- •hypersensitivity to acyclovir,
- •pregnant woman,
- •participation in another clinical study in the last two months
- •volunteers with ongoing viral HSV/VZV infection treated with acyclovir,
- •adults under guardianship or other legal protection, deprived of their liberty by judicial or administrative decision
研究组 & 干预措施
acyclovir
Subjects take a single dose of 5 mg/kg infused over 1 hour.
干预措施: Acyclovir (Drug)
结局指标
主要结局
Renal elimination clearance
时间窗: Day 1
To quantify the relationship between lean body mass, measured by Dual-energy x-ray absorptiometry (DEXA), and the true absolute glomerular filtration rate (GFRa) which is estimated by the renal elimination clearance of acyclovir.
次要结局
- the qualitative compilation of adverse events associated with acyclovir infusion observed and reported by the volunteer.(Day 1, Day 2)
- the interindividual variability of acyclovir exposure : glomerular filtration rate(Day 1)
- the interindividual variability of acyclovir exposure : lean mass(Day 1)