Determination of dose‐dependent absorption of amoxycillin from urinary excretion data in healthy subjects.

Chulavatnatol, Suvatna; Charles, B. G.

doi:10.1111/j.1365-2125.1994.tb04353.x

Cited by 29 publications

(20 citation statements)

References 13 publications

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“…The comparatively low clearance in our patients may be attributed largely to immature renal function because the kidneys account for the elimination of up to three-quarters of the dose in healthy adults. 4,15 In very premature neonates, this unchanged fraction is likely to be even higher because of concomitantly impaired liver function 6,17 (however, measurement of the renal clearance of amoxicillin was not possible in the present study because urine samples could not be obtained). There was a significant decrease of ∼25% in amoxicillin CL with coadministered gentamicin, although any dose effects could not be studied because all infants received the same dose (2.5 mg/kg).…”

Section: Discussionmentioning

confidence: 83%

“…Firstly, because a significantly different population of amoxicillin CL could be clearly identified very soon after gentamicin was discontinued (i.e., during the remaining 1-2 days of amoxicillin administration); and second, the premature newborn is thought to be less susceptible to gentamicin-induced renal toxicity than older pediatric patients and adults. 7,18,19 It is also unlikely that renal tubular secretion, which normally accounts for a large fraction of amoxicillin excretion in adults, 4,15,21 was inhibited by gentamicin. Tubular secretion is believed to be very inefficient in the newborn.…”

Section: Discussionmentioning

confidence: 97%

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Population Pharmacokinetics of Intravenous Amoxicillin in Very Low Birth Weight Infants

Charles¹,

Preechagoon²,

Lee³

et al. 1997

Journal of Pharmaceutical Sciences

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The population pharmacokinetics of amoxicillin were determined in 40 very premature infants (< or = 32 week gestational age, < 1500 g birth weight) who were receiving intravenous amoxicillin (50 mg/ kg, every 12 h) during the first days after birth. Serum amoxicillin concentrations were measured by HPLC. Clearance (CL) and volume of distribution (Vd) were modeled alone and under the influence of demographic and clinical covariates with a 1-compartment model with first-order elimination. The final population models with influential covariates were: CL(L/h) = 0.0000610 x body weight (g) and CL (L/h) = 0.0000805 x body weight (g), for infants also receiving gentamicin and not receiving gentamicin, respectively; Vd(L) = 0.678. The interpatient standard deviation (SD) for CL was 0.0351 L/h, and for Vd was 0.365 L. The intrapatient variability (SD) among observed and model-predicted serum concentrations was 13.7 mg/L. Evaluation of the predictive performance of this model in another group of infants (n = 16) indicated statistically insignificant bias (p > 0.05) of 3 mg/L among pairs of observed and Bayesian-predicted amoxicillin concentrations. The average population CL was smaller, but the average Vd and terminal half-life (t1/2) were larger than previously reported for healthy adults.

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Section: Discussionmentioning

confidence: 83%

Section: Discussionmentioning

confidence: 97%

Population Pharmacokinetics of Intravenous Amoxicillin in Very Low Birth Weight Infants

Charles¹,

Preechagoon²,

Lee³

et al. 1997

Journal of Pharmaceutical Sciences

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“…30) In the present study, plasma and tissue concentrations showed linearity, despite the administration of large amoxicillin doses (50, 25 mg/kg). The amoxicillin concentrations were affected only when amoxicillin was associated with sodium diclofenac.…”

Section: )mentioning

confidence: 78%

Effect of Sodium Diclofenac on Serum and Tissue Concentration of Amoxicillin and on Staphylococcal Infection

Groppo

Simões

Ramacciato

et al. 2004

Biological & Pharmaceutical Bulletin

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Amoxicillin is a widely prescribed aminopenicillin, primarily for oral use.1) Ninety percent of the administered dose is absorbed without molecular modifications.2) It provides human serum concentration ranging from 7.6 mg/ml to 10.8 mg/ml when 500 mg/p.o. is used 3,4) ; 15.1 mg/ml when 15.4 mg/kg/p.o. is used, 1) and 14.5 mg/ml when 40 mg/kg/p.o. is used.5) The serum concentrations in rats were 28 mg/ml and 13 mg/ml when amoxicillin doses of 40 mg/kg/p.o. and 7.0 mg/kg/p.o. were administered, respectively. 6,7)

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“…Numerous factors could be responsible for these conflicting findings, including the use of different dose formulations (tablet vs capsule vs liquid), varying sample stability following collection, and variability in analytical accuracy as well as type and volume of liquid used to administer the oral dosage form. [36] This variability within and between studies may simply reflect the importance and relative impact of intestinal pH on the rate and amount of amoxicillin intestinal absorption. Under normal physiologic conditions, i.e.…”

Section: Discussionmentioning

confidence: 99%

Variations in Amoxicillin Pharmacokinetic/Pharmacodynamic Parameters May Explain Treatment Failures in Acute Otitis Media

Pichichero¹,

Reed

2009

Pediatric Drugs

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Pharmacokinetic/pharmacodynamic (PK/PD) modeling and Monte Carlo simulations suggest that amoxicillin should rarely fail as therapy for Streptococcus pneumoniae and Haemophilus influenzae acute otitis media (AOM) infections except when the S. pneumoniae are highly penicillin resistant or the H. influenzae are beta-lactamase producing. However, important and not infrequent exceptions to this expectation have been described. The objective of this review was to define the biologic variations in amoxicillin PK/PD parameters for the treatment of AOM in children and assess whether these variations could explain why the commonly employed amoxicillin PK/PD model is imperfect in predicting outcome for every patient in this clinical setting. To this end, a literature search of MEDLINE (1966-2006) and EMBASE (1974-2006) was conducted to identify studies that evaluated ampicillin or amoxicillin intestinal absorption, serum concentrations, and/or middle ear fluid (MEF) concentrations. Analysis of studies identified for review showed that the intestinal bioavailability of amoxicillin depends on passive diffusion and a saturable 'pump' mechanism that produces variable serum concentrations of the antibacterial agent. Indeed, substantial differences from patient to patient in serum (5- to 30-fold) and MEF (up to 20-fold) concentrations of amoxicillin occur following oral administration, and 15-35% of children have no detectable amoxicillin in MEF. These findings suggest that variability in PK/PD parameters may impact amoxicillin concentrations in serum and MEF, possibly explaining some AOM treatment failures.

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Determination of dose‐dependent absorption of amoxycillin from urinary excretion data in healthy subjects.

Cited by 29 publications

References 13 publications

Population Pharmacokinetics of Intravenous Amoxicillin in Very Low Birth Weight Infants

Population Pharmacokinetics of Intravenous Amoxicillin in Very Low Birth Weight Infants

Effect of Sodium Diclofenac on Serum and Tissue Concentration of Amoxicillin and on Staphylococcal Infection

Variations in Amoxicillin Pharmacokinetic/Pharmacodynamic Parameters May Explain Treatment Failures in Acute Otitis Media

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