Pharmacokinetics of a Fluoronaphthyridone, Trovafloxacin (CP 99,219), in Infants and Children following Administration of a Single Intravenous Dose of Alatrofloxacin

Abstract

The pharmacokinetics of trovafloxacin following administration of a single intravenous dose of alatrofloxacin, equivalent to 4 mg of trovafloxacin per kg of body weight, were determined in 6 infants (ages 3 to 12 months) and 14 children (ages, 2 to 12 years). There was rapid conversion of alatrofloxacin to trovafloxacin, with an average ؎ standard deviation (SD) peak trovafloxacin concentration determined at the end of the infusion of 4.3 ؎ 1.4 g/ml. The primary pharmacokinetic parameters (average ؎ SD) analyzed were volume of distribution at steady state (1.6 ؎ 0.6 liters/kg), clearance (151 ؎ 82 ml/h/kg), and half-life (9.8 ؎ 2.9 h). The drug was well tolerated by all children. There were no age-related differences in any of the pharmacokinetic parameters studied. Less than 5% of the administered dose was excreted in the urine over 24 h. On the basis of the mean area under the concentration-time curve of 30.5 ؎ 10.1 g ⅐ h/ml and the susceptibility (<0.5 g/ml) of common pediatric bacterial pathogens to trovafloxacin, dosing of 4 mg/kg/day once or twice daily should be appropriate.

Pharmacokinetics and Pharmacodynamics of the New Quinolones

“…A number of investigators have studied the pharmacokinetics of the new quinolones in special populations. [90][91][92][93][94] In the elderly, it has been demonstrated that the pharmacokinetics (eg, bioavailability) of levofloxacin, gatifloxacin, and moxifloxacin are not appreciably affected. 16,22,34,92 The pharmacokinetics of levofloxacin remain unchanged in patients with acquired immunodeficiency syndrome (AIDS) in relation to healthy adults.…”

Synthesis and Biological Evaluation of New Amino Acid and Dipeptide Derivatives of Neocryptolepine as Anticancer Agents

“…Several l - and d - amino acids were introduced into the anthraquinone skeleton, and numerous derivatives were synthesized for the evaluation of the anticancer activity. For example, such conjugates as conjugates of doxorubicin, daunorubicin, and mitoxantrone with an amino acid or peptides show more selective antitumor activity than the drugs themselves. − The attachment of an amino acid or a peptide to the drug can also increase the solubility in water of the new compound. , …”

Fluoroquinolones in Pediatrics

“…The pharmacology of trovafloxacin in children has also been analyzed in two clinical trials [10,11]. The results of these studies indicated that a dose of 4 mg/kg is required to achieve serum levels similar to those achieved after a 300 mg intravenous dose of trovafloxacin in adults and that cerebrospinal fluid (CSF) concentrations were approximately 25% of the serum levels with peak CSF levels above the minimum inhibitory concentration (MIC) of most pathogens involved in the etiology of bacterial meningitis in children.…”