Clarithromycin pharmacokinetics in healthy young and elderly volunteers.
The pharmacokinetics of clarithromycin and its active 14(R)-hydroxy metabolite were assessed in 12 healthy young and 12 healthy elderly volunteers after oral administration of a multiple dose regimen of oral clarithromycin (500 mg every 12 hours for 5 doses). Plasma and urine clarithromycin and 14(R)-hydroxyclarithromycin concentrations were determined using high-performance liquid chromatography. The elderly subjects exhibited significantly elevated clarithromycin peak (Cmax) and trough (Cmin) plasma concentrations and area under the plasma concentration-time curve (AUC) compared with young subjects. In addition, the elderly group exhibited a significantly reduced apparent total body clearance (300 +/- 97 versus 476 +/- 112 mL/min, respectively) and renal clearance (CLR) (84 +/- 31 versus 168 +/- 35 mL/min, respectively). Similar results were noted for the 14(R)-hydroxy metabolite, with significantly elevated Cmax, Cmin, and AUC and reduced CLR in the elderly compared with the young group. Because the differences in parent and metabolite pharmacokinetic parameters were small and the increase in circulating drug concentrations was well tolerated (no increase in incidence or severity of adverse events), adjustments in clarithromycin dosing regimens may not be necessary solely on the basis of age.
Chu
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SY
Drug Metabolism Department, Abbott Laboratories, Abbott Park 60064-3500.
Wilson
D S
DS
Guay
D R
DR
Craft
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C
D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D002851:Chromatography, High Pressure Liquid; D017291:Clarithromycin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives / Q000493:pharmacokinetics*; D003404:Creatinine / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D008657:Metabolic Clearance Rate
C056228:14-hydroxyclarithromycin; D003404:Creatinine; D017291:Clarithromycin