Intra‐ and inter‐individual variation in pharmacokinetics of intravenously infused amoxycillin and ampicillin to elderly volunteers.

Abstract

1 The purpose of this study was to investigate the disposition of two aminopenicillins and their intra-and inter-individual variation in pharmacokinetic parameters in healthy, elderly volunteers. Two groups, each of 12 active, community-dwelling volunteers between 69 and 83 years of age participated. One group was given 500 mg of amoxycillin, the other group 500 mg of ampicillin as single i.v. infusions. Within the drug groups each volunteer was given the infusion at two different occasions separated by a time-period of 1 week. Amoxycillin and ampicillin were determined in plasma and urine by modern column liquid chromatographic methods.2 The mean plasma clearance was about 200 ml min-' 1.73 m2 for both drugs and renal clearance accounted for approximately 80% of this. As expected, drug clearance was correlated to renal function as determined by 5tCr-EDTA. The volume of distribution at steady-state (V.,) was about 0.3 1 kg-' for both drugs. Compared to our previous results in younger subjects, plasma and renal clearances were essentially similar in this study, but slightly longer half-lives and higher V. were seen for amoxycillin and ampicillin.3 The intra-individual variation, expressed as the error of a single determination (CV), was small, for plasma clearance 3.7% and 6.4% after amoxycillin and ampicillin. The corresponding inter-individual variation in clearance was higher, 14.4% after amoxycillin, and 11.9% after ampicillin. The results confirm a higher relative efficiency of a crossover vs a completely randomized parallel groups design in parenteral studies of these penicillins. 4 In our elderly subjects there was only an approximately 30% decrease in renal function. This was not enough to reduce the drug clearance and offers an explanation for the similarity between our present results in the elderly and our previous results in younger subjects. Elderly volunteers may be different from patients with disease as a confounding factor. Studies on elderly active and community-dwelling volunteers, as in this study, may therefore be more representative as to the effect of age per se on drug kinetics.

Nonlinearity of amoxicillin absorption kinetics in human

“…Thus, the absorption of amoxicillin appears too irregular to be generally described by a simple first-order or zero-order process. By contrast, a successful fit of a two-compartment disposition model to the IV data was obtained, confirming the previous report on the stability of the disposition of amoxicillin [19].…”

Bone Penetration of Amoxicillin and Clavulanic Acid Evaluated by Population Pharmacokinetics and Monte Carlo Simulation

“…Therefore, prior knowledge of the structural PK model and the average disposition parameters for the serum concentration profiles and their variability from published studies (4,5,29,30,49,51) were incorporated in the present analyses. As those studies were conducted with young healthy volunteers, the amoxicillin clearance reported by Sjovall et al (53) for elderly subjects was used. This was in agreement with the age-related decrease in renal function predicted by the formula of Cockcroft and Gault (13) on the basis of the CL values from the other studies.…”

Characterization of the Population Pharmacokinetics of Ampicillin in Neonates Using an Opportunistic Study Design

“…The PK of ampicillin have been studied in children and adults (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14), but data on dosing in the neonatal population are sparse. Current dosing regimens take into account the gestational age (GA)-and postmenstrual age (PMA)-related variation in renal drug clearance and recommend lower doses and less frequent dosing in the most premature neonates (1).…”