| Hepatic kinetics of SCP-1 (N-[alpha-(1,2-benzisothiazol-3(2H)-ona-1, 1-dioxide-2-yl)-acetyl]-p-aminophenol) compared with acetaminophen in isolated rat liver. | |
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MedLine Citation:
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PMID: 9885301 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The hepatic disposition of a new analgesic, SCP-1, a derivative of acetaminophen, was studied in the isolated perfused rat liver using a recirculating system. The aim of this study was to compare the kinetic parameters of this molecule with those of acetaminophen. Sprague-Dawley rat (230-330 g) livers were perfused for 2 h with 250 ml Krebs-Henseleit bicarbonate buffer containing SCP-1 or acetaminophen, 0.07 mmol l(-1) (n=4), 0.28 mmol l(-1) (n=4), and 0.8 mmol l(-1) (n=4) (approximately one, four and ten times the therapeutic doses in man, respectively). Perfusate samples were collected from the efflux at various times. The SCP-1 and acetaminophen perfusate concentrations were assayed by a HPLC method. Pharmacokinetic analysis was carried out using a computer program. There were significant differences between the hepatic kinetics of SCP-1 and those of acetaminophen. Thus, SCP-1 elimination half-life (mean 14.8+/-10.0 min) was shorter than that of the acetaminophen (186.1+/-27.7 min) (t=11.6, P=0.0001). While the half-life of SCP-1 increases with concentration, the half-life of acetaminophen remains constant as the concentration increases. The hepatic clearance was higher for SCP-1 than acetaminophen (mean 19.01+/-14.5 ml min(-1) vs. 1.29+/-0.08 ml min(-1), respectively) (t=2.44, P<0.05), and it behaved according to dose-dependent kinetics. The SCP-1 extraction ratio was higher (mean 0.63+/-0.49) than for acetaminophen (0.04+/-0.01) (t=2.41, P<0.05) and this parameter tended to decrease as the perfusate concentrations of SCP-1 increased. It was concluded that the hepatic kinetics of SCP-1 behaved according to dose-dependent kinetics, and statistically significant differences were found between pharmacokinetics parameters of both drugs studied. |
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Authors:
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G González-Martin; C Lyndon; C Sunkel |
Publication Detail:
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Type: Comparative Study; Journal Article |
Journal Detail:
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Title: European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft für Pharmazeutische Verfahrenstechnik e.V Volume: 46 ISSN: 0939-6411 ISO Abbreviation: Eur J Pharm Biopharm Publication Date: 1998 Nov |
Date Detail:
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Created Date: 1999-04-01 Completed Date: 1999-04-01 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 9109778 Medline TA: Eur J Pharm Biopharm Country: NETHERLANDS |
Other Details:
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Languages: eng Pagination: 293-7 Citation Subset: IM |
Copyright Information:
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Copyright 1998 Elsevier Science B.V. |
Affiliation:
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Catholic University of Chile, Santiago, Chile. ggonzale@puc.cl |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Acetaminophen
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analogs & derivatives*,
pharmacokinetics* Analgesics, Non-Narcotic / pharmacokinetics* Animals Area Under Curve Dose-Response Relationship, Drug Liver / metabolism* Male Perfusion Rats Rats, Sprague-Dawley Saccharin / analogs & derivatives*, pharmacokinetics |
| Chemical | |
Reg. No./Substance:
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0/Analgesics, Non-Narcotic; 0/SCP 1; 103-90-2/Acetaminophen; 81-07-2/Saccharin |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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