Intravenous omeprazole in children: pharmacokinetics and effect on 24-hour intragastric pH.

BACKGROUND: Omeprazole is a proton pump inhibitor, acting selectively on the gastric parietal cell H+K+-adenosine triphosphatase. Data on the intravenous route are limited in children and not available in infants. OBJECTIVE: This study was designed to determine the pharmacokinetics and the optimal dosage of intravenous omeprazole in patients younger than 30 months of age. METHODS: Nine children (three girls), aged 4.5 to 27 months, with normal liver and renal functions requiring intravenous omeprazole were studied. After enrollment in the study and randomization, omeprazole was administered once daily, at 8 am, as a 1-hour infusion. Group 1, consisting of the first four patients, received 20 mg/1.73 m2, and group 2, consisting of the following five patients, received 40 mg/1.73 m2. At day 3, a 24-hour intragastric pH and a pharmacokinetic study of omeprazole were performed. Plasma concentrations were measured by high-performance liquid chromatography. RESULTS: Patients in group 2 had a significantly higher median pH (6.99 vs. 3.35; P = 0.01) and percent of monitored time with gastric pH >4 than children given 20 mg/1.73 m2 (90.6% vs. 44.8%; P < 0.01). Four had a pH more than 4 during more than 90% of the time versus none of the patients of group 1. The plasma concentration versus time curves showed rapid elimination of the drug. The median area under the curve of omeprazole was 0.78 microg. mL-1. h-1 (range, 0.55-1.64 microg. mL-1. h-1) and 3.95 microg. mL-1. h-1 (range, 1.9-4.9 microg. mL-1. h-1), respectively, in groups 1 and 2 (P < 0.05). Systemic clearance was not different between the two groups: median values were 0.68 and 0.42 L. kg-1. h-1 (P = 0.22). CONCLUSIONS: In critical situations, intravenous administration of omeprazole may be required in infants. The authors demonstrate that the dose of 20 mg/1.73 m2 is not effective in maintaining 24-hour gastric pH of more than 4 and that a dose of 40 mg/1.73 m2 is required.

Lansoprazole in children: pharmacokinetics and efficacy in reflux oesophagitis.

BACKGROUND: Data on the proton pump inhibitor lansoprazole in paediatric patients are limited. AIM: To investigate the pharmacokinetics, optimal dosage and efficacy of lansoprazole in paediatric patients. METHODS: A 24-h gastric pH recording and a pharmacokinetic study were performed after 7 days of lansoprazole, 17 mg/m2, in 23 patients with reflux oesophagitis (median age, 3.5 years). Response was defined as pH > 3 for > 65% of the recording. The dosage was doubled in non-responders. Patients with no response on day 14 were excluded. Responders underwent endoscopy after 4 weeks on the response-inducing dosage; abnormal findings led to a repeat endoscopy after four additional weeks. RESULTS: Nine patients responded to 17 mg/m2 and six to 30.3 mg/m2. On day 7, time with pH > 3 was significantly correlated with the area under the plasma concentration-time curve (P=0.003). The area under the plasma concentration-time curve was significantly greater in the nine responders to 17 mg/m2 than in the 14 other patients. Pharmacokinetic parameters were similar in responders and non-responders to the higher dose. After 4 weeks, oesophagitis was healed in 80% of responders. Adverse events occurred in three patients and required treatment discontinuation in one. CONCLUSIONS: Lansoprazole is effective and safe in children. The optimal starting dosage is 30 mg/m2 or 1.4 mg/kg.

Synergism between interleukin-6 and interleukin-1beta in hypothalamic serotonin release: a reverse in vivo microdialysis study in F344 rats.

The effects of interleukin-1beta (IL-1beta) and interleukin-6 (IL-6) perfused locally into the anterior hypothalamus (AHY) on serotonin (5-hydroxytryptamine, 5-HT) release were investigated in the same region using in vivo microdialysis in conscious, freely moving F344 rats. IL-1beta (1 ng/rat) or IL-6 (50 ng/rat) injected directly into the AHY elicited a rapid and transient statistically significant increase in extracellular 5-HT levels (to 161% and 145% of the respective AUC (area under the curve) basal value, 100%). Intra-hypothalamic infusion of IL-1-receptor antagonist IL-1Ra (2 mug/rat) prevented this effect of IL-1beta, but not that of IL-6, suggesting an IL-1beta-independent mechanism for hypothalamic 5-HT release by this latter cytokine. Furthermore, intra-hypothalamic co-perfusion of IL-6 with IL-1beta at sub-optimal doses (10 ng/rat and 0.5 ng/rat, respectively) synergized in releasing hypothalamic 5-HT, thus providing in vivo evidence that both cytokines, IL-6 and IL-1beta are able to modulate the neuronal 5-HT response in the rat AHY.