Comparative bioavailability characteristics of commercial quinidine polygalacturonate and sulfate tablets.

This study compared the relative bioavailability characteristics of quinidine polygalacturonate (QP) and quinidine sulfate (QS) after oral administration of commercial tablets and a liquid form prepared from crushed tablets in 13 healthy adult male volunteers. Each subject received the following four single-dose treatments in a randomized, crossover manner with a one-week washout period between treatments: 400 mg QS liquid, two 200-mg QS tablets, 550 mg QP liquid, and two 275-mg QP tablets. All four treatments were equivalent in terms of the dose of quinidine base. Multiple serum samples and two 24-hour urine specimens were collected over 24 and 48 hours, respectively, and assayed for quinidine with a specific HPLC assay method. For the absorption and disposition parameters measured (maximum serum concentration, time to reach maximum concentration, area under the concentration-time curve [0-48 hours], absorption and elimination rate constants, absorption and elimination half-lives, apparent total body clearance, apparent volume of distribution, and dose fraction excreted in the urine) no significant differences were observed for any of the parameters among the four treatments (p greater than 0.05). The results of the present investigation demonstrated that QP and QS produced identical serum quinidine concentration-time curves when given in the form of a tablet or liquid. The clinical implications of these observations with respect to the dosing of QP are discussed.

[Experimental study of the antitumor properties and mechanism of action of kortifen]. / Eksperimental'noe izuchenie protivoopukholevykh svoistv i mekhanizma deistviia kortifena.

Cortiphen, a newly developed hormonal cytostatic ester of 11-desoxy-17 alpha-hydroxycorticosterone and chlorophenacyl, is described. It was studied in transplantable, spontaneous and induced tumors of 7 sites: hemoblastosis (5), hepatoma (3), mammary gland (5), lung (2), gastrointestinal tract (3), sarcoma (2) and melanoma. Practically all the tumors were shown to respond to cortiphen action. Among the antitumor effects of the drug were: long-term inhibition of tumor growth or tumor regression, contribution to longer survival, antimetastatic action and sustained action during repeated courses of administration. Cortiphen was found to interact with glucocorticoid receptors in both animal and human tumors. The role of the hormonal component of the drug's molecule in the realization of its antitumor effect is discussed.

[Intraindividual comparison of the elimination kinetics of Lipofundin S and Intralipid in consecutive lipid tolerance tests]. / Intraindividueller Vergleich der Eliminationskinetik von Lipofundin S und Intralipid in aufeinanderfolgenden Fettoleranztests.

Two intravenous fat tolerance tests (IVFTT) were performed in 16 healthy volunteers and 8 patients suffering from hypertriglyceridemia (HTG). We compared Lipofundin S (Braun, Melsungen) with Intralipid (Kabi Vitrum, Stockholm), using both 10- and 20% concentrations. Time intervals between the tests were 1 h for the volunteers and 2 h for the patients with HTG, respectively. Fractional elimination rates were obtained from light scattering intensity of serum samples. They were significantly higher for Lipofundin S (9.61%/min for healthy men and 12.48%/min for healthy women) compared to Intralipid (7.09%/min for healthy men and 9.41%/min for healthy women). This difference occurred independently of (1) serum triglyceride concentrations and sex of the volunteers, (2) concentrations of lipid emulsions (10 vs. 20%), and (3) the test sequence (Lipofundin S or Intralipid first). This means that the elimination kinetics during an IVFTT are not influenced by a foregoing test. Similar features of both emulsion types were: (1) Faster elimination in women compared to men, and in healthy volunteers compared to HTG patients; (2) inverse correlation between fractional elimination rates and serum triglyceride concentrations. Fractional elimination rates of Lipofundin S and Intralipid were closely interrelated. Obviously there exists an intra-individually characteristic elimination capacity for exogenous triglycerides.

Pharmacokinetics and bacteriological efficacy of ticarcillin-clavulanic acid (timentin) in experimental Escherichia coli K-1 and Haemophilus influenzae type b meningitis.

The pharmacokinetics and bacteriological efficacy of ticarcillin and clavulanic acid administered individually or in combination were assessed in rabbits with experimental Escherichia coli K-1 and Haemophilus influenzae type b meningitis. The mean penetrations into the cerebrospinal fluid (CSF) of infected animals after a single dose of ticarcillin-clavulanic acid were approximately 11 and 28% for ticarcillin and clavulanic acid, respectively. In continuous-infusion experiments, the mean penetrations into CSF were 14.6 and 35% for ticarcillin and clavulanic acid, respectively, in rabbits with E. coli meningitis and 6.1 and 24%, respectively, in rabbits with H. influenzae meningitis. In animals that received a continuous infusion of the two drugs alone or in combination, the median CSF bactericidal titers for E. coli were less than 1:2, less than 1:2, and 1:2 for ticarcillin, clavulanic acid, and ticarcillin-clavulanic acid, respectively, and for H. influenzae the titers were less than 1:2, less than 1:2, and 1:4, respectively. The addition of clavulanic acid potentiated significantly the bacteriological efficacy of ticarcillin in reducing the number of bacteria in CSF of infected rabbits. Additional studies in animals and humans are required before recommendations can be made regarding the use of ticarcillin-clavulanic acid for treatment of meningitis.

Ofloxacin versus trimethoprim-sulphamethoxazole in acute cystitis.

The clinical and bacteriological efficacy and adverse reactions of ofloxacin vs trimethoprim-sulphamethoxazole were investigated in a double-blind, randomised study in 250 female patients (125 in each group) with acute, uncomplicated lower urinary tract infections. The dosages of ofloxacin and trimethoprim-sulphamethoxazole were 100mg and 160mg + 800mg twice daily, respectively. The duration of therapy was 3 days. 81% of the patients had significant bacteriuria. Escherichia coli was isolated in 76% and Staphylococcus saprophyticus in 11% of the infections. The bacteriological elimination, clinical cure and improvement rates of the evaluable patients on ofloxacin treatment were 92 and 95%, respectively. The corresponding figures on trimethoprim-sulphamethoxazole therapy were 88 and 90%. Adverse reactions were clinically unimportant, and none of the patients had to stop treatment. Mild and transient side effects, mainly from the gastrointestinal tract, central nervous system and skin, were reported by 19 and 22% of the patients in the ofloxacin and trimethoprim-sulphamethoxazole groups, respectively. None of the differences in clinical and bacteriological efficacy and side effects of ofloxacin vs trimethoprim-sulphamethoxazole were statistically significant. Ofloxacin appears to be an appropriate antibiotic for short term therapy of acute, uncomplicated, lower urinary tract infections, comparing favourably with trimethoprim-sulphamethoxazole treatment in this study.