Pharmacokinetics of a clarithromycin suspension in infants and children

Abstract

The single-and multiple-dose pharmacokinetics of clarithromycin and its 14-(R)-hydroxylated metabolite in infants and children were studied after oral administration under fasting and nonfasting conditions. Drug absorption appeared to be rapid following a brief delay in its onset; the mean peak concentrations in plasma (C..,1) for clarithromycin were reached within about 3 h under both conditions. The mean Cm. for Clarithromycin (6-o-methylerythromycin) is a new macrolide antibiotic which differs from erythromycin only by methyl substitution at the 6-hydroxy position of the 14-membered macrolide ring. The difference in structure results in improved gastric acid stability, increased gastrointestinal tolerance (7), and increased spectrum of antibacterial activity against a variety of aerobic and anaerobic gram-positive and gram-negative organisms compared with erythromycin (1, 5). After an oral dose, a substantial fraction of the absorbed dose of clarithromycin undergoes first-pass metabolism through the liver to form the active 14-(R)-hydroxylated metabolite. This 14-hydroxylated metabolite has been reported to be more active than clarithromycin against multiple strains of Haemophilus influenzae (4), which is important in the consideration of using this drug in children.Pharmacokinetic studies performed with adult volunteers with the tablet formulation have shown that clarithromycin has a more favorable pharmacokinetic profile than erythromycin. Clarithromycin was rapidly absorbed, reaching peak concentrations in plasma approximately 2 h after dosing. Its concentration-time profiles in plasma were adequately described by using the one-compartment model, but the underlying disposition kinetics were nonlinear and the half-life appeared to be dose dependent (6).Because clarithromycin has potential usefulness for treatment of a variety of infectious conditions, the pharmacokinetics of clarithromycin and its metabolite in infants and children who were given the oral suspension formulation were investigated. MATERIAILS AND METHODSPatients. The study was conducted in the outpatient clinic of Children's Medical Center, Dallas, Tex. Infants and children aged 6 months to 10 years, with pharyngitis, otitis media, or skin infections and for whom an orally administered antibiotic had been prescribed were considered eligible for the study. The parents or guardians of each patient were * Corresponding author.informed of the nature of the study, and written consent was obtained prior to enrollment in the study. The exclusion criteria were a history of hypersensitivity to macrolide antibiotics, renal or hepatic impairment, and concomitant administration of other medications such as antibiotics, theophylline, carbamazepine, or digitalis.Children were assigned to receive the clarithromycin suspension according to one of the following treatment regimens. Groups 1 and 2 received the clarithromycin suspension at 7.5 mg/kg of body weight once, group 1 under fasting conditions and group 2 under nonfasting states. The fasting condition...

In vitro susceptibilities of spotted fever group rickettsiae and Coxiella burnetti to clarithromycin

“…(8,10,17,41), and Toxoplasma gondii (3,7,12). In comparison with erythromycin, clarithromycin showed improved pharmacokinetic properties, including the maximum concentration of drug in the serum of patients treated with up to 4 p,g/ml (9,19), and a high intracellular concentration of the drug, with intracellular to extracellular concentration ratios of 30 to 40 (2).…”

“…Children (5) improved pharmacological and pharmacokinetics properties compared with those of erythromycin and because it is well tolerated during childhood and pregnancy. Previous studies have shown that clarithromycin may reach concentrations in serum of up to 4 ,ug/ml (9,19) and that it is highly concentrated within eukaryotic cells (2).…”

Clinical Pharmacokinetics of Clarithromycin

“…When clarithromycin was administered as a suspension (7.5 mg/kg body weight) to 24 infants and children. mean Cmax values reached 3.59 11g/mL (5).…”

“…a decreased dose or prolonged dosing intervals may be appropriate (17). In infants and children, 7.5 mg/kg body weight bid seems appropriate (5). (In Canada, clarithromycin is currently indicated for adults and children above 12 years of age.…”

Intra-Species Extrapolation in Risk Assessment of Different Classes of Antimicrobials

“…Meal content was standardized throughout the study. The results obtained from this study were compared to the results obtained by Gan et al (1992), who studied the pharmacokinetics of clarithromycin suspension in infants and children. One group studied comprised 10 children (7 M, 3 F; age 0.5 to 10.2 years (mean 3.0 years); mean weight 14.1 kg).…”