Study of the pharmacokinetics and pharmacodynamic activity of almitrine bismesylate in infants during the recovery phase following bronchopulmonary dysplasia.
The efficacy and pharmacokinetics of almitrine bismesylate were studied in 6 infants (age 2.5-9.5/months) during the recovery phase following bronchopulmonary dysplasia. The infants did not require assisted ventilation, but needed oxygen therapy with an FiO2 of 25-30% in stable condition. One to three hours after a single oral dose of almitrine (1.5 mg/kg), there was a marked increase in transcutaneous PO2 (TcPO2) (mean 2kPa) followed by a regular decrease to the baseline level. Nine to fourteen days after repeated administration of almitrine (1.5 mg/kg/12 h) in 4 children, the mean gain in TcPO2 was only 0.85 kPa. There was a very early flagging in efficacy of almitrine, since none of the children could be weaned from oxygen therapy. The absorption peak occurred 1-3 h after the administration of the compound. The maximum almitrine concentration was 173 +/- 44 ng/ml; plasma clearance was 21.9 +/- 6.6 ml/min and the volume of distribution was 18.7 +/- 2.1 liters/kg. The drug was eliminated biphasically. In the 4 studies with repeated drug administration, the pharmacokinetic results suggested that a steady state was still not achieved after 9-14 days of treatment. These results and the absence of any sustained effect of repeated doses of the drug raise the problem of a particular type of almitrine metabolization in the infant.
D000284:Administration, Oral; D015765:Almitrine; D001997:Bronchopulmonary Dysplasia / Q000378:metabolism*; D000697:Central Nervous System Stimulants / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D010879:Piperazines / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology
D000697:Central Nervous System Stimulants; D010879:Piperazines; D015765:Almitrine