Role of mononuclear phagocytes in decreased hepatic drug metabolism following administration of Corynebacterium parvum.
Explore the source record for details and available documents.
Biomedical subjects
Publications and source records attributed to L F Soyka.
Explore the source record for details and available documents.
The role of caffeine and other methylxanthines in prematurity, intrauterine growth retardation, and the respiratory distress syndrome is currently under investigation. Their pharmacokinetics are discussed together with their newly discovered beneficial role as possible inhibitors of premature labor and accelerators of fetal lung maturation.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Previous studies have shown that acute administration of methadone to male rats prior to mating results in adverse effects on their progeny, particularly decreased birth weights and increased neonatal mortality. Rather than chronic administration accentuating these effects, results of the present study indicate that tolerance developed so that no adverse effects were found in offspring sired after 21--32 days of methadone administration. In the sire, maintenance of normal weights of accessory sex glands after 4 months of daily methadone suggests that tolerance developed to the CNS effect(s) responsible for the depressed serum LH and testosterone levels found after acute administration of narcotics. In contrast, tolerance did not develop to the inhibition of weight gain produced by methadone administration. No evidence for a dominant lethal effect could be found after chronic methadone administration, in contrast to suggestive evidence for this effect found in previous experiments after acute methadone administration.
Transcutaneous PO2 (tcPO2) monitoring offers a new approach to the evaluation of drug effects. We investigated the effect of theophylline on ten premature infants with apnea. Theophylline was administered as aminophylline, 8 mg/kg per rectum every 12 hours for two doses and 4 mg/kg every 12 hours for a total of two or five days (short and long courses). The tcPO2, heart rate (beat-to-beat), and thoracic impedance were continuously monitored during each of three 4-hour study periods: 12 hours before theophylline administration, 12 hours after initiation of theophylline therapy, and 24 to 48 hours after discontinuing the drug's use. Plasma levels were measured by a radioimmunoassay developed in our laboratory. Polygraphic recordings were analyzed without knowledge of treatment for frequency of apneic spells, mean duration of apneas, total duration of hypoxemia (tcPO2 less than or equal to 40 torr), total duration of hyperoxemia (tcPO2 greater than or equal to 100 torr), basal tcPO2, heart rate, and respiratory rate. In each case during theophylline use, cardiorespiratory patterns were altered, respirations were more regular, apneic spells were reduced, PO2 was stabilized with less hypoxia and hyperoxia, and bradycardic episodes were decreased. There was considerable variation in the response of the ten infants and a significant difference in the frequency of return of symptoms between those receiving short-term therapy and those receiving the longer course.
The use of theophylline in premature infants has necessitated the development of an assay applicable to samples under 0.1 ml. To accomplish this we have developed a radioimmunoassay for theophylline. The antiserum to theophylline has been characterized and found to be highly specific for theophylline and sensitive to 2 ng. The affinity of our antibody and the titer developed in the goat allowed the assay to be performed routinely with the use of a plasma sample size of only 2 to 5 micronl. Theophylline levels of 6 to 20 microng/ml were found 2 hr after maintenance doses of aminophylline, 4 mg/kg per rectum in 12 premature infants. Terminal serum half-lives ranged from 12 to 54 hr.
The LD50 of aminophylline in adult mice differed from young mice and rats of both ages, in which the values were remarkably similar (Table 1). With the exception of fat, which had lower concentrations in all groups, tissue concentrations after a 4 mg/kg rectal dose of aminophylline in the 10-day-old animals ranged from 10-20 microng/g as compared to 4-10 microng/g in the adults (Table 2). To evaluate preferential distribution, an analysis of tissue to blood concentration ratios was made. All ratios approximated 1.0 except fat which had a ratio of 0.1-06. The neonates of each species had significantly higher tissue to blood ratios for brain, heart, small intestine, skeletal muscle, and fat (P less than 0.05). Brain to plasma and brain to blood ratios were very similar ranging from 0.4-1.3 in adults versus 0.8-1.7 in neonates. Consideration of the time course indicated a trend toward unit, with the overall ratio in both groups being 1.15 at 2 hr. However, at all earlier time periods the ratios were clearly higher in neonates. Administration of aminophylline intraperitoneally to produce serum concentrations of theophylline far in excess of the 10-20 microng/ml considered to be safe and effective in clinical use did not decrease bilirubin levels in young or old Gunn rats (Fig. 1).
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Injections of killed suspensions of Corynebacterium parvum (i.p.) in young male mice were followed by time- and dose-dependent decreases in the drug-metabolizing activity of liver microsomes and lung homogenates. In vitro assays with model substrates [aminopyrine, aniline, p-nitroanisole, and benzo(a)pyrene] were used to quantitate drug-metabolizing activity. It is likely that such decreases in mixed function oxidases activity will act to significantly alter the pharmacokinetics of concurrently or subsequently administered drugs. The results provide a possible mechanism to explain several previously reported immunochemotherapeutic interactions.
We have observed that ingestion of methadone (METH) by male rats prior to mating greatly increased the neonatal death rate of their offspring. In this experiment male rats were allowed drinking water containing METH for 24 hrs, alone or in the presence of females, and then mated with drug-naive females. When both males and females were exposed to METH the frequency of matings was decreased. Offspring of METH males were lighter in weight at birth and at weaning, particularly if their sires had been exposed to females during the period of METH ingestion. Although the neonatal death rate of the METH offspring was more than twice that of controls this difference was not statistically significant. The enhancement of METH effects by concurrent exposure to females leads us to propose that the locus of action of METH is the developing spermatozoa.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
The concentrations of digoxin in tissues of premature infants, full-term infants and older children obtained at autopsy were determined by a radioimmunoassay procedure. Infants were found to have much higher concentrations in the right and left ventricle (about 190 ng/g) than older children (about 70 ng/g) and adults as reported in the literature. Renal concentrations were lower in the premature group which may be related to their limited excretory capacity for digoxin. The relatively high myocardial concentrations of digoxin found in this study suggest that the usually recommended doses for infants may be excessive.