Description<\/h3>\n\n\n\n
Theophylline is used in the treatment of \nreversible airway obstruction due to chronic asthma, chronic bronchitis,\n or COPD. Both the bronchodilator and the adverse effects are closely \nrelated to drug concentration.\n<\/p>\n\n\n\n
Theophylline is well absorbed<\/a> when taken orally as a rapid-release tablet or when administered as a liquid solution. Bioavailability<\/a> and rate of absorption<\/a> of controlled-release<\/a> preparations are more variable and influenced by formulation and food intake. \n<\/p>\n\n\n\n Theophylline distributes<\/a>\n rapidly into fat-free tissues and body water. 40% is bound to plasma \nproteins, primarily to albumin, although blood pH values, the plasma \nprotein content and the administration of concomitant drugs may vary \nthis fraction. Theophylline passes freely across the placenta, into \nbreast milk and into cerebrospinal fluid.\n<\/p>\n\n\n\n Theophylline is primarily eliminated by hepatic \nmetabolism involving isoenzymes of the cytochrome P450 system. This \nmetabolism has been assumed to follow first order kinetics (in some \npatients, nonlinear kinetics<\/a> may be observed at therapeutic concentrations). Age and disease are the major endogenous factors influencing metabolism: clearance<\/a>\n is markedly reduced in the neonates and elderly and increased in the \nfirst decade of life. Cirrhosis reduces clearance of theophylline, as \ndoes congestive heart failure. Exogenous factors such as concomitantly \nadministered drugs, smoking and nutritional factors affect \nbiotransformation by inducing or inhibiting<\/a>\n the metabolizing enzymes: low-carbohydrate and high protein diet, \nactive and passive smoking are associated with a significant increase in\n theophylline clearance. \n<\/p>\n\n\n\n Renal elimination<\/a>\n of unchanged drug accounts for 10 to 15% of the total elimination of \nthe dose in adults and may increase to up to 50% in neonates. Therefore,\n in a normal adult, renal disease has no significant effect on \ntheophylline clearance.<\/p>\n\n\n\n Estimation of the individual theophylline clearance<\/a>\n should take into account the patients concomitant diseases, age and \ndrug therapy. In patients with cor pulmonale, cardiac failure or end \nstage liver dysfunction, theophylline should be avoided if possible.\n<\/p>\n\n\n\n Because of intra- and inter-individual variability<\/a>\n in the pharmacokinetics of theophylline, which may be increased by the \npresence of endogenous and\/or exogenous factors, it is suitable to \nsupervise theophylline therapy by therapeutic drug monitoring<\/a> (TDM) for the target concentrations to be achieved.<\/p>\n\n\n\n Rifampicin is used in the treatment of tuberculosis. It may also be used in the treatment of other infectious diseases such as in the eradication of meningococci from healthy carriers. Because of the ease with which many pathogens develop resistance to rifampicin monotherapy, it is often used in combination with other antibacterial drugs. <\/p>\n\n\n\n Rifampicin undergoes rapid and complete absorption<\/a>\n after oral administration. Absorption is improved when the oral dose is\n taken on an empty stomach, as food may decrease the rate of absorption \nof rifampicin. Rifampicin absorption is very sensitive to changes in product formulation<\/a>. \n<\/p>\n\n\n\n Rifampicin undergoes wide distribution<\/a>\n into most body tissues and fluids, including the cerebrospinal fluid. \nIt has a unique property of penetrating intracellularly. The protein \nbinding is approximately 80%. Rifampicin crosses the placenta and may be\n found in maternal milk.\n<\/p>\n\n\n\n Rifampicin is extensively eliminated by intestinal and hepatic metabolism<\/a>. The drug and its metabolites are largely excreted<\/a> in bile and eliminated in stools. Rifampicin undergoes enterohepatic recirculation<\/a> as does its metabolites. Only a small proportion of the dose is excreted unchanged in the urine<\/a> (15-25%), giving the urine an orange color.\n<\/p>\n\n\n\n Since rifampicin is a potent enzyme inducer<\/a> of the cytochrome P450 oxidase system, its administration is associated with numerous drug interactions<\/a>. Rifampicin also has an inducer effect on its own hepatic metabolism. Therefore, repeated administration<\/a> of rifampicin increases its oral clearance<\/a>\n by inducing its own gut and hepatic metabolism or enhancing its biliary\n excretion. Rifampicin also induces the activity of the \nglucuronyltransferases, sulphotransferases and the efflux transporter \nP-glycoprotein.<\/p>\n\n\n\n Because of the potential for drug interactions<\/a>,\n patients receiving concomitant therapies which may be altered by \nrifampicin should be monitored closely to ensure efficacy of these \ntherapies.\n<\/p>\n\n\n\n Use with caution and modify dosage regimen<\/a> in patients with liver impairment, as metabolism<\/a> can be significantly altered with marked reduced hepatic function, especially when used in combination with other hepatotoxins, (e.g. isoniazid) or inhibitors (e.g. antiretroviral drugs). No dose adjustments are needed for renal dysfunction or dialysis.<\/p>\n\n\n\n Theophylline pharmacokinetic parameters Oral bioavailability (F) 96% Clearance (CL) 3 L\/h Volume of Distribution (Vd) 35 L Half-life (t1\/2) 8 h Description Theophylline is used in the treatment of reversible airway obstruction due to chronic asthma, chronic bronchitis, or COPD. Both the bronchodilator and the adverse effects are closely related to drug concentration. Theophylline is … <\/p>\nClinical implications<\/h3>\n\n\n\n
Clinical implications<\/h3>\n\n\n\n
![\"\"](\"https:\/\/sepia2.unil.ch\/pharmacology\/wp-content\/uploads\/2019\/07\/graphTheoohylline.png\")
<\/figure><\/div>\n<\/div>\n\n\n\n![\"\"](\"https:\/\/sepia2.unil.ch\/pharmacology\/wp-content\/uploads\/2019\/07\/graphTheoohylline1-1.png\")
<\/figure><\/div>\n<\/div>\n<\/div>\n\n\n\nTheophylline pharmacokinetic parameters <\/h4>\n\n\n\n
Induce metabolism significantly<\/strong><\/td> Inhibit metabolism significantly<\/strong><\/td><\/tr> Phenobarbital <\/td> Cimetidine <\/td><\/tr> Phenytoin <\/td> Ciprofloxacin <\/td><\/tr> Rifampicin <\/td> Disulfuram <\/td><\/tr> Hydrocarbons (smoke) <\/td> Oral contraceptives <\/td><\/tr> <\/td> Propanolol <\/td><\/tr> <\/td> Erythromycin <\/td><\/tr> <\/td> Fluvoxamine <\/td><\/tr><\/tbody><\/table>\n","protected":false},"excerpt":{"rendered":"