The pharmacokinetics of ceftiofur sodium were determined in domestic chicks, turkey poults, adult cockatiels (Nymphicus hollandicus), and adult orange-winged Amazon parrots (Amazona amazonica) after subcutaneous (chicks and turkey poults and intramuscular (i.m.) dosing (cockatiels and Amazon parrots). Turkey poult data were best fit to a single exponential model with disappearance half-lives (t1/2) of 8.6, 7.4 and 5.6 h after doses of 0.12, 0.24 and 0.48 mg ceftiofur free acid equivalents (CFAE)/poult, respectively. Data from chicks were best fit to a biexponential model with primary and secondary half-lives of 2.2 and 7.5, 3.7 and 6.8, and 3.8 and 5.3 h after doses of 0.04, 0.08 and 0.16 mg CFAE/chick, respectively. Cockatiel and Amazon parrot data were best fit to a biexponential model with primary and secondary half-lives of 0.28 and 2.5, and 0.93 and 7.9 h, respectively, after doses of 10 mg CFAE/kg body weight. The maximum concentration (Cmax) and area under the concentration time curve (AUC) in chicks and poults were dose-proportional. The Cmax for cockatiels was 5.2 micrograms/mL and for Amazon parrots was 11 micrograms/mL. Clearance in cockatiels and Amazon parrots were 11.3 and 3.8 mL/min/kg, respectively, and reflected the much greater AUC seen in Amazon parrots. Clearance values of ceftiofur were similar in chicks and Amazon parrots, slightly greater in turkey poults and greatest in cockatiels. These results indicate that pharmacokinetic differences must be considered when establishing dosage regimens for different avian species.

Microbial transformation studies were conducted with the antitumor alkaloid thalicarpine. Streptomyces punipalus (NRRL 3529) converted thalicarpine to (+)-hernandalinol, the structure of which was determined spectroscopically and by synthesis from the known alkaloid hernandaline. This unusual biotransformation reaction most likely occurs by oxidative cleavage of the isoquinoline ring from thalicarpine through the intermediate hernandaline, which then undergoes further reduction to hernandalinol.

No abstract

3-Ethylidino-2-oxo-1,4-benzodioxane (23). Reaction of catechol with 5b at 25°for 72 hr in the presence of KI gave 23 (18% yield): mp 74-75°(95% ethanol); nmr (CDCI3) 6.99 (s, 4, aro-

Halo Michael acceptors react with catechol in aprotic solvents in the presence of potassium carbonate to form 2-substituted 1,4-benzodioxanes. Cis 0-alkyl and 0-alicyclic -halo Michael acceptors yield primarily cis 2,3-disubstituted 1,4-benzodioxanes, whereas trans 2,3-disubstituted isomers predominate when catechol is treated with trans 0-alkyl -halo Michael acceptors. It is therefore inferred that the reaction proceeds via a cis Michael addition of catechol monoanion, followed by intramolecular nucleophilic displacement of halide from the newly generated sp3 a carbon by the remaining catechol oxygen. Ethyl l,4-bromobut-2-enoate, formed by isomerization of ethyl 2-bromobut-2-enoate during the course of the reaction of the latter with catechol, is believed to be the source of the isomeric ethyl l,4-benzodioxanyl-2-acetate isolated as a minor product.