| N-acetyl-L-gamma-glutamyl derivatives of p-nitroaniline, sulphamethoxazole and sulphamethizole for kidney-specific drug delivery in rats. | |
| | |
MedLine Citation:
|
PMID: 9643438 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
Kidney-specific delivery of p-nitroaniline, sulphamethoxazole and sulphamethizole after either intravenous administration of the L-gamma-glutamyl or N-acetyl-L-gamma-glutamyl derivatives or the parent drugs has been examined in a rat model. All L-gamma-glutamyl derivatives were converted to the corresponding parent drugs within 60 min whereas the N-acetyl-L-gamma-glutamyl derivatives were fairly stable in the systemic circulation after parenteral administration. Concentrations of p-nitroaniline and sulphamethoxazole 20 min after administration of the parent drugs were somewhat higher in the kidney than in the liver and lung. The concentration of sulphamethizole in the kidney was dramatically higher than those in the hepatic and pulmonary tissue. Kidney-specific delivery of the drugs of interest was evaluated by determining the tissue concentrations of the released parent drug and the total drug levels (i.e. drug levels after hydrolysis of all conjugate to the parent drug). For L-gamma-glutamyl-p-nitroaniline released renal levels of p-nitroaniline and total p-nitroaniline concentrations were both higher than those obtained after p-nitroaniline dosing. Use of L-gamma-glutamylsulphamethoxazole resulted in higher total sulphamethoxazole concentrations in the kidney, but did not lead to an increase in released (unconjugated) sulphamethoxazole levels. In contrast, no kidney-selective distribution was observed for L-gamma-glutamylsulphamethizole. Markedly increased kidney distribution was observed for both N-acetyl-L-gamma-glutamyl-p-nitroaniline and N-acetyl-L-gamma-glutamylsulphamethoxazole and the liver and lung concentrations were correspondingly reduced in comparison with parent drug dosing. Use of the N-acetyl-L-gamma-glutamyl-p-nitroaniline conjugate increased the concentration of p-nitroaniline in the kidney to the same extent as did L-gamma-glutamyl-p-nitroaniline. In conclusion, N-acetyl-L-gamma-glutamyl derivatization of certain compounds seems to be useful for kidney-specific drug delivery and preliminary data suggests that lipophilic drugs are better substrates than hydrophilic compounds. Results related to the selectivity of tissue distribution of the derivatives and species differences are discussed. |
| | |
Authors:
|
T Murakami; K Kohno; R Yumoto; Y Higashi; N Yata |
Related Documents
:
|
10714838 - The pharmacokinetics of anesthetic drugs and adjuvants during cardiopulmonary bypass. 21182488 - Novel and emerging drugs for acute myeloid leukemia: pharmacology and therapeutic activ... 3220888 - Isolation of basic drugs from plasma using solid-phase extraction with a cyanopropyl-bo... 19797608 - Prediction of v(ss) from in vitro tissue-binding studies. 11201798 - Changes in lipid and protein constituents of rafts and caveolae in multidrug resistant ... 17020598 - Malaria treatment failures after artemisinin-based therapy in three expatriates: could ... |
Publication Detail:
|
Type: Journal Article |
Journal Detail:
|
Title: The Journal of pharmacy and pharmacology Volume: 50 ISSN: 0022-3573 ISO Abbreviation: J. Pharm. Pharmacol. Publication Date: 1998 May |
Date Detail:
|
Created Date: 1998-09-21 Completed Date: 1998-09-21 Revised Date: 2003-11-14 |
Medline Journal Info:
|
Nlm Unique ID: 0376363 Medline TA: J Pharm Pharmacol Country: ENGLAND |
Other Details:
|
Languages: eng Pagination: 459-65 Citation Subset: IM |
Affiliation:
|
Department of Biopharmaceutics, Institute of Pharmaceutical Sciences, Hiroshima University School of Medicine, Japan. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Aniline Compounds
/
administration & dosage,
pharmacokinetics* Animals Anti-Infective Agents / administration & dosage, pharmacokinetics* Drug Delivery Systems Injections, Intravenous Kidney / metabolism* Liver / metabolism Lung / metabolism Male Prodrugs / administration & dosage, pharmacokinetics* Rats Rats, Wistar Sulfamethizole / administration & dosage, analogs & derivatives, pharmacokinetics* Sulfamethoxazole / administration & dosage, analogs & derivatives, pharmacokinetics* Tissue Distribution |
| Chemical | |
Reg. No./Substance:
|
0/Aniline Compounds; 0/Anti-Infective Agents; 0/Prodrugs; 100-01-6/4-nitroaniline; 144-82-1/Sulfamethizole; 723-46-6/Sulfamethoxazole |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Polymeric chitosan-based vesicles for drug delivery.
Next Document: The effect of a drug-delivery system consisting of soybean phosphatidyl choline and medium-chain mon...