Cyclacillin is a semisynthetic penicillin produced from the penicillin nucleus (6-aminopenicillanic acid) by acylation with 1-aminohexanecarboxylic acid. The absorption and excretion characteristics of cyclacillin were defined in one completely randomized and three three-way crossover experiments. Mean peak serum cyclacillin levels appeared earlier and were fivefold higher than those obtained with equal doses of ampicillin. High serum cyclacillin concentrations were reached at 0.5 h and by 2 h were lower than ampicillin. Serum ampicillin concentrations peaked at 1.5 h, remaining slightly higher than those for cyclacillin for the next 4.5 h. The mean area for the cyclacillin curve was significantly superior to either of the ampicillin formulations. Mean serum concentrations of cyclacillin exhibited a smooth dose-response, approximately doubling in each instance as the dose was doubled from 250 to 500 and from 500 to 1,000 mg. High concentrations of cyclacillin were also demonstrated in urine. Neither ratio of drug to metabolite in the urine nor the percent of excretion was significantly affected by the dose level. Sixty-seven percent of the drug was excreted unchanged, and 17% was excreted as penicilloic acid, with most of the excretion occurring within 6 h of administration. In subjects given 500 mg of cyclacillin (four times daily) for 6 days, 2% of the drug was excreted as 1-aminocyclohexanecarboxylic acid, and approximately 55% (24 to 91%) was unchanged. Neither formation nor excretion of the former was sex dependent.Cyclacillin is a semisynthetic penicillin produced from the penicillin nucleus (6-aminopenicillanic acid) by acylation with 1-aminocyclohexanecarboxylic acid. The empiric formula of cyclacillin is C16H2,,08NS. Its structural forgiula is shown in Fig. 1.Like ampicillin, cyclacillin is a broad-spectrum penicillin which is bactericidal against a variety of gram-positive and gram-negative organisms, is not significantly inhibited by serum protein (less than 25% bound), and exhibits a stepwise pattern of resistance (7). Unlike ampicillin, it shows appreciable resistance to penicillinase, retaining 64% of its activity after 10 min of incubation at 37 C with staphylococcal penicillinase; by contrast, ampicillin is completely inactivated under the same conditions (7). It also appears to produce serum and urinary concentrations in human subjects which are considerably higher than those produced by equivalent oral doses of ampicillin (6,8). These latter properties have not been fully elaborated in the literature. The present communication, therefore, reports on a series of investigations which were conducted to provide data on serum and urinary concentrations of cyclacillin in humans. METHODS AND MATERIALSCyclacillin and ampicillin. Cyclacillin was prepared as 250-mg tablets and as oral suspensions of 125 and 25Q mg per 5 ml; ampicillin was prepared as 250-mg tablets and 250-mg capsules. Iodometric and microbiological assays were performed for each of the preparations.Serum and urine assays. Serum specimen...
The anterior pituitary gland regulates physiological processes via the secretion of hormones, which are under the control of factors produced either in the hypothalamus or the pituitary gland itself. Studies investigating how the pituitary gland functions have employed both in vitro and in vivo approaches. Although in vitro analysis has the advantage that it is pituitary specific, the results may be incomplete because the tissue is isolated from other physiological inputs that could affect function under natural conditions. Without vascular input, such studies are inherently of short duration. Conversely, in vivo experiments that rely upon systemic hormone injections require high doses, are non-target specific and the precise hormone concentrations reaching the pituitary gland are difficult to control. Intracerebroventricular hormone infusions are reliant on assumptions that factors are transported to the pituitary gland from the cerebrospinal fluid and are without cerebral effects. Here we describe an innovative method to investigate anterior pituitary function in conscious sheep by direct infusion of peptides into the pituitary tissue surrounding the hypophyseal portal blood vessels. This approach is an adaptation of the hypophyseal portal cannulation technique whereby an indwelling cannula provides direct access to the rostral aspect of the adenohypophysis. Peptide infusions were achieved by insertion of a needle through the implanted cannula such that it penetrated the pituitary. Using this technique, infusion of TRH (17ng/1μl/min for up to 6h) induced a sustained rise in systemic prolactin levels that lasted for the duration of the infusion.
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