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.

An unequal cross-over event within the CYP2D gene cluster generates a chimeric CYP2D7/CYP2D6 gene which is associated with the poor metabolizer phenotype.

1. The study of the CYP2D genotype and phenotype of a Caucasian family revealed that a XbaI-9 kb allele was associated with the poor metabolizer phenotype. 2. A Polymerase Chain Reaction (PCR)-based assay showed that the previously described mutations D6A and D6B are not associated with the XbaI-9 kb allele. 3. To explore the molecular basis of the poor metabolizer phenotype associated with the XbaI-9 kb allele, complete sequencing of the nine exons and intron-exon boundaries of the CYP2D6 gene was undertaken after amplification by PCR. 4. All the exons were successfully amplified using CYP2D6 gene-specific primers except exon 1 which required a combination of CYP2D7 gene-specific 5' primer and a CYP2D6 gene-specific 3' primer. 5. Sequence data derived from this amplified product revealed that the XbaI-9 kb allele corresponds to a novel rearrangement of the locus. This involved a deletion of an approximately 20 kilobase (kb) DNA segment generating a hybrid 5' CYP2D7/CYP2D6 3' gene. 6. The chimeric gene is non-functional presumably due to an insertion in exon 1 (characteristic of the exon 1 of the CYP2D7 gene) which causes a shift in the reading frame with premature termination of translation.