Nocturnal Profile of Growth Hormone Secretion during Sleep Induced by Zolpidem: A Double-Blind Study in Young Adults and Children

Abstract

Overnight blood sampling for repeated growth hormone (GH) assays, regarded as the most physiological assessment of GH status, may induce some disturbances in patients’ sleep and then in the evaluation of GH secretion. We studied the influence of a hypnotic drug, zolpidem (10 mg), on nocturnal GH profiles (GH peak, time to first and maximum GH peak, area under the curve, mean integrated concentration) over two nights at a 7-day interval, in a double-blind cross-over design in a group of 12 young adult volunteers (27.9 ± 4.3 years), and in a group of 12 children (10.8 ± 2.3 years) with short stature, in a parallel double-blind study. Mean GH profiles showed no difference between zolpidem-treated subjects and placebo-treated controls, either in adults or in children. Although in these experimental conditions, sleep onset latency was significantly reduced with zolpidem in the adult volunteers, the mean time to first GH peak remained unchanged. Furthermore, GH profile did not relate with sleep duration, sleep onset latency or number of awakenings. A hypnotic drug, such as zolpidem, given at bedtime, is therefore devoided of effect on nocturnal GH profile and may be used in young children for overnight blood sampling when needed.

Potential Pharmacokinetic Basis for Zolpidem Dosing in Children With Sleep Difficulties

“…As expected, both C max and AUC increased significantly when the dose was increased from 0.125 to 0.25 mg/kg and finally to 0.5 mg/kg. This finding is consistent with the pharmacokinetics of zolpidem in adult patients, 33 , 34 , 35 , 36 , 37 , 38 which have demonstrated dose proportionality over the dose range 2.5–40 mg.…”

“…As expected, both C max and AUC increased significantly when the dose was increased from 0.125 to 0.25 mg/kg and finally to 0.5 mg/kg. This finding is consistent with the pharmacokinetics of zolpidem in adult patients, [33][34][35][36][37][38] which have demonstrated dose proportionality over the dose range 2.5-40 mg. No significant dose effect was found for any other pharmacokinetic parameters evaluated. T max (1.1 h, SD ¼ 0.6, CV 54.5%) was extremely stable across dose and age groups and is consistent with observations from studies in adults; mean T max ¼ 1.5 h (range ¼ 0.75-2.6 h).…”

Zolpidem for Persistent Vegetative State - A Placebo-Controlled Trial in Pediatrics

“…The order of treatment periods was randomly assigned by a pharmacist, to either 4 daily doses of zolpidem or 4 daily doses of placebo given in a double-blinded manner. The dosage range for zolpidem was 0.14 -0.2 mg / kg [8,15,17] . The capsule containing either zolpidem or placebo was administered either orally or via gastrostomy tube, with parents instructed to mix the contents of the capsules with water to fl ush through the gastrostomy.…”