Single-dose pharmacokinetics of a novel oral platinum cytostatic drug ([OC-6-43]-bis[acetato][1-adamantylamine]amminedichloroplatinum [IV]) in pigs
Language English Country Spain Media print
Document type Comparative Study, Journal Article, Research Support, Non-U.S. Gov't
PubMed
15632953
DOI
10.1358/mf.2004.26.9.872565
PII: 872565
Knihovny.cz E-resources
- MeSH
- Amantadine administration & dosage analogs & derivatives metabolism pharmacokinetics MeSH
- Administration, Oral MeSH
- Time Factors MeSH
- Chemistry, Pharmaceutical methods trends MeSH
- Feces chemistry MeSH
- Swine, Miniature MeSH
- Organoplatinum Compounds administration & dosage metabolism pharmacokinetics MeSH
- Platinum blood urine MeSH
- Area Under Curve MeSH
- Half-Life MeSH
- Swine MeSH
- Drug Evaluation, Preclinical MeSH
- Antineoplastic Agents administration & dosage chemistry pharmacokinetics MeSH
- Reproducibility of Results MeSH
- Drug Administration Schedule * MeSH
- Animals MeSH
- Check Tag
- Female MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Comparative Study MeSH
- Geographicals
- Czech Republic MeSH
- Names of Substances
- Amantadine MeSH
- bis(acetato)(1-adamantylamine)amminedichloroplatinum(IV) MeSH Browser
- Organoplatinum Compounds MeSH
- Platinum MeSH
- Antineoplastic Agents MeSH
The pharmacokinetics of total platinum (Pt) were investigated after a single oral dose of (OC-6-43-bis(acetato)(1-adamantylamine)amminedichloroplatinum (IV) (LA-12). A dose of 3 mg/kg (n = 3) and 30 mg/kg (n = 3) was given to two parallel groups of pigs (n = three each). Pt was measured in the blood, urine and feces by atomic absorption spectrometry. Blood was sampled at specified times until 240 h, urine was obtained through a catheter at 1-h intervals until 6 h, and feces were collected until 240 h after administration. LA-12 was rapidly absorbed, as indicated by a T(max) of total Pt within 0.5-1.5 h after administration. The mean (SEM) values for maximum plasma concentration (0.060 +/- 0.025 and 0.39 +/- 0.08 mg/l) and the area under the plasma concentration vs. time curve (12.6 +/- 5.6 and 36.3 +/- 2.0 mg.h/l) increased less than proportionally to the increase in the dose. The mean (SEM) Pt urinary excretion determined over a 6-h postdose period achieved only 1.9% and 0.8% of the administered doses, respectively. Within 2 h after dosing, the renal clearance of total Pt was approximately 2-fold higher than that of creatinine (CL(cr)). Thereafter, it steadily dropped and in the last collection interval (5-6 h postdose) its value was 50% less than CL(cr). Platinum recoveries in feces over 10 days after dosing reached 0.4% and 2.6% of the administered dose, respectively. This finding indicates that the extent of absorption of both doses was high. There were no changes in results of hematology and clinical biochemistry tests.
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