Pharmacokinetics of intravenous theophylline in Jordanians

Pharmacokinetics of intravenous theophylline were investigated in fifteen healthy adult, male, non-smoking, Jordaninan volunteers. A short aminophylline infusion was administered [4.3 mg/kg theophylline] over 15 minutes. Serum theophylline levels were measured using a fluorescence polarization immunoassay. At the end of infusion, serum theophylline levels were [mean +/- SEM] 10.5 +/- 1.2 micro g/ml. The serum concentration-time data were best fit by a one compartment open model. Pharmacokinetic parameters were: Mean theophylline elimination half-life [t1/2] was 10.03 +/- 0.65 hr; apparent volume of distribution [Vd] was 0.46 +/- 0.0058 L/kg and clearance was 0.031 +/- 0.002 L/kg. The theophylline elimination half-life reported in this investigation is longer than what was reported in most of the previous studies in Western populations. The reason for this is not known, however, it may be due to differences in dietary habit and/or environmental factors

Dose response effect of cimetidine on the elimination of theophylline

The effects of constant plasma levels of cimetidine given by exponential infusion specially designed to give constant plasma levels of 0,1,2,4 and 6 g/ ml on the elimination kinetics of theophylline and its metabolites were studied in seven healthy young non-smoker Caucasian volunteers aged 27 +/- 1.2 year. Cimetidine effects started at 1 micro g/ml and gradually increased to a maximum effect at 6 g/ml, the maximum decreases in theophylline clearance was 18% and maximum increase in elimination half-life was 38% [p<0.05]. Cimetidine effects on the theophylline metabolites were also tested; 3-methylxanthine plasma levels were greatly affected and were dose dependent as tested by ANOVA [p<0.05], its plasma AUC decreased by maximum value of 53% [p<0.05] and the fraction of its elimination in urine decreased by a maximum value of 48% [p<0.001]. In contrast, cimetidine effects on 1-methyluric acid and 1,3-dimethyluric acid were not significantly different from controls

Comparative analysis of theophylline by fluorescence polarization immunoassay [FPIA] and high performance liquid chromatography

The fluorescence polarization immunoassay [FPIA] was used to estimate serum theophylline levels from fifty patients. These results were compared with those obtained by high performance liquid chromatography [HPLC]. The data obtained by FPIA were comparable with those obtained by HPLC method [r 0.9425]. The coefficient of variaion, percentage of bias intra- and inter-day variablity were similar in both methods. In conclusion the results obtained by the two methods are similar

Anaphylactic reactions during intravenous urography

Out of 4261patients from the Jordan University Hospital and Al-Islamic Hospital, Amman Jordan, five patients developed serious anaphylactoid reactions after intravenous injection of iodinated radiographic contrast medium [RCM] within the past 18 months. Two patients were above 55 years of age with a history of ischemic heart disease, two others gave a history of allergy; one to fish and the other to RCM [urografin] [R] and the 5th patient was a young female without a previous history of allergy or significant illness. In this retrospective study, the present situation concerning the aetiology of RCM reactions, dangers, precautions and treatment are thoroughly discussed

Physiological basis and clinical relevance of drug interactions with cimetidine

It is now well recognized that coadministration of cimetidine can alter the pharmacokinetic disposition of many drugs, and that this can result in either an altered therapeutic response, or induce a toxic response to the drug. Inhibition of oxidative metabolism is the most widely recognized mechanism for such a drug: drug interaction. However, cimetidine can alter drug absorption, distribution, metabolism and renal elimination of other drugs. This review discusses the mechanisms by which cimetidine can influence normal drug disposition and describes available information about specific drug whose disposition has been shown to be altered by cimetidine, and indicates the potential clinical relevance of such interaction

Applications of a new technique to achieve and maintain a rapid and constant plasma cimetidine concentration I

A new system has been employed in this experiment to achieve and maintain a rapid and constant plasma drug concentration. There is an excellent agreement between the in-vitro results fig. 3 and the in-vivo results table 3; these results obtained using the exponential infusion system provides a good approach that can be used in experimental work and can be applied clinically in the intensive care unit

Cimetidine decreases theophylline elimination II

This study examines the effect of intravenous cimetidine administration on aminophylline elimination. Aminophylline [4.3 mg/kg] was administered by short intravenous infusion both before and after cimetidine administration. Cimetidine was administered by exponential infusion system to achieve and maintain a concentration of 4.0 micro g/mI in the plasma. Plasma samples were collected before and at various hours for 12 hours after each aminophylline administration, and theophylline concentrations were measured by an HPLC system. Cimetidine significantly decreased theophylline clearance p < 0.03, and increased theophylline elimination half life p < 0.05. The apparent volume of distribution was not altered by cimetidine administration. Cimetidine may slow theophylline elimination by inhibition of the hepatic microsomal monoxygenase system, which could be clinically significant and cause serious side effects. The effect of cimetidine on metabolic pathways of theophylline is the objective of future study

Mechanism of resistance to the effects of glucagon on cAMP accumulation and ketogenesis in hyperthyroid rats

The mechanism of resistance in hypothyroidism to the effects of glucagon was examined utilizing isolated hepatocytes prepared from male rats made hypothyroid with propyithiouracil [PTU]. The increased activity of the low Km phosphodiesterase in hepatocytes from hypothyroid animals may be responsible for the decline in cAMP concentration, since the addition of methylisobutylxanthine [MIX] to the incubation medium restored the effects of glucagon on cAMP accumulation and ketogenesis in hepatocytes from hypothyroid animals to the same levels as those in the euthyroid control group. The sensitivity to glucagon in both groups was increased. The response to 8-Bromo-cAMP was biphasic, At 10[9] M 8-Bromo-cAMP ketogenesis was significantly lower in hepatocytes from hypothyroid rats than euthyroid. The maximal response to 8-Bromo-cAMP was, however, similar in hepatocytes from either euthyroid or hypothyroid animals