Fluphenazine enanthate and fluphenazine decanoate: Intramuscular injection and esterification as requirements for slow-release characteristics in dogs
✍ Scribed by Jacques Dreyfuss; James M. Shaw; John J. Ross Jr
- Book ID
- 102914330
- Publisher
- John Wiley and Sons
- Year
- 1976
- Tongue
- English
- Weight
- 701 KB
- Volume
- 65
- Category
- Article
- ISSN
- 0022-3549
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✦ Synopsis
0 ''C-Fluphenazine base was administered intramuscularly in sesame oil to five male beagles (2 mg/kg). The concentration of radioactivity in plasma and the excretion of radioactivity in urine and feces were measured for 14 days. Maximum concentrations of radioactivity were found in plasma 2 hr after administration. These levels declined with elimination half-lives of 3.20 hr during the 2-12-hr interval after dosing and of 4.02 days during the 2-14-day interval. Most administered radioactivity was excreted during the first 2 days after dosing, predominantly in the feces. An average of 0.43% of the dose was present at the injection site 14 days after dosing; some residual radioactivity was found in the liver and in the ocular portion consisting of the combined retina, choroid, and sclera. ''C-Fluphenazine and its enanthate and decanoate esters were each administered intravenously to three different groups of intact dogs at doses of 1 mg/kg. Regardless of which compound was administered, concentrations of radioactivity in the plasma of these dogs were comparable. Thirty minutes after these dogs had been dosed with I4C-fluphenazine enanthate or ''C-fluphenazine decanoate, most radioactivity in the plasma was present as I4C-fluphenazine base and other unidentified metabolites; at this time, at least 79% of either of the two I4Cfluphenazine esters had been biotransformed. The excretion of radioactivity by these same three groups of dogs was very similar, regardless of which of the three compounds was given. In 7 days, an average of only 3 4 % of the dose was excreted in urine; the remainder was excreted in feces. ''C-Fluphenazine and its enanthate and decanoate esters (1 mg/kg) were administered intravenously to dogs whose bile ducts had been cannulated. The amounts of radioactivity excreted in the urine and bile in 8 hr were very similar, as were the residual amounts of radioactivity present in selected tissues. Comparison of the data obtained from dogs given these three compounds intravenously (unformulated) or intramuscularly in sesame oil points to the following conclusions: ( a ) fluphenazine base per se does not provide slow-release characteristics unless it has been esterified, for example, with heptanoic or decanoic acid, and (b) intramuscular rather than intravenous administration of these two esters is responsible for producing their slow-release characteristics.
Keyphrases Fluphenazine-base, enanthate, and decanoate esters, comparison of slow-release characteristics, effect of route of administration, dogs Pharmacokinetics-fluphenazine base, enanthate, and decanoate, comparison of slow-release characteristics, effect of route of administration, dogs Excretion-fluphenazine base, enanthate, and decanoate, comparison of slow-release characteristics, effect of route of administration, dogs 0 Tranquilizers-fluphenazine base, enanthate, and decanoate esters, comparison of slow-release characteristics, effect of route of administration, dogs NCS solubilizer, Arnersham/Searle Corp..