RE: Covariate Models Using Weight
From: "Piotrovskij, Vladimir [JanBe]" <VPIOTROV@janbe.jnj.com>
Subject: RE: Covariate Models Using Weight
Date: Tue, 23 Nov 1999 11:36:22 +0100
I agree, it is already too long, but still, one more reason for not to rely very much on SCR and CLCR (irrespective to the formula used). Creatinine is excreted partly via an active process, tubular secretion, and its steady-state level may be affected by some drugs. One example I have found is given at the end of my mail. I presume there are more recent examples.
Vladimir
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Vladimir Piotrovsky, Ph.D.
Janssen Research Foundation
Clinical Pharmacokinetics
B-2340 Beerse
Belgium
Email: vpiotrov@janbe.jnj.com
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Authors
Cahen R. Martin A. Francois B. Baltassat P. Louisot P.
Institution
Division of Nephrology, Lyon-South University Medical Center, Pierre Benite,
France.
Title
Creatinine metabolism impairment by an anticonvulsant drug, phenacemide.
Source
Annals of Pharmacotherapy. 28(1):49-51, 1994 Jan.
MeSH Subject Headings:
Adult
*Anticonvulsants/ae [Adverse Effects]Carbamazepine/tu [Therapeutic Use]
Case Report
*Creatinine/bl [Blood]
Epilepsy, Temporal Lobe/bl [Blood]
Epilepsy, Temporal Lobe/dt [Drug Therapy]
Glomerular Filtration Rate
Human
Male
Phenobarbital/tu [Therapeutic Use]
*Urea/aa [Analogs & Derivatives]
Urea/ae [Adverse Effects]
Abstract:
OBJECTIVE: To report two cases of increased true serum creatinine (Scr) without renal failure caused by an anticonvulsant drug, phenacemide, and to discuss the possible mechanisms. CASE SUMMARY: Two patients treated with phenacemide were investigated for markedly increased Scr and decreased creatinine clearance (Clcr) values. Glomerular filtration rates, as determined by 125I-iothalamate clearance, were normal in both patients and analytical interferences with the Jaffe reaction were excluded. After discontinuation of the drug, phenacemide concentrations became undetectable within 2 days but it took 7-14 days for Scr and Clcr to return to normal values. DISCUSSION: The Scr increase with phenacemide (120-170 percent) was higher than that reported with cimetidine or trimethoprim (10-40 percent) and could not be explained solely by inhibition of the tubular secretion of creatinine. The hypothesis of an overproduction of creatinine caused by phenacemide was ruled out by experimental studies in rats. Creatinine increase in tissues was lower than that in the serum of rats given phenacemide. In vitro creatinine influx into red blood cells was inhibited in a dose-dependent way by phenacemide. CONCLUSIONS: Increased Scr concentrations in these patients could be related to an inhibition of transport and a decrease in creatinine volume of distribution. Creatinine concentrations should not be considered when dosage adjustments of renally eliminated drugs are being calculated for patients with such metabolic interferences.
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Other thread subtopics:
Centering Covariates
Covariate Models Using Weight (Allometric Scaling)
Covariate Models Using CrCL