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CLINICAL PHARMACOLOGY
Dyphylline is a xanthine derivative with pharmacological actions similar to theophylline and other members of this class of drugs. Its primary action is that of bronchodilation, but it also exhibits peripheral vasodilatory and other smooth muscle relaxant activity to a lesser degree. The bronchodilatory action of dyphylline, as with other xanthines, is through to be mediated through competitive inhibition of phsphodiesterase with a resulting increase in cyclic AMP producing relaxation of bronchial smooth muscle.
Dyphylline is well tolerated and produces less nausea than aminophylline and other alkaline theophylline compounds when administered orally. Unlike the hydrolyzable salts of theophylline, dyphylline is not converted to free theophylline in vivo. It is absorbed rapidly in therapeutically active form and in healthy volunteers reaches a mean peak plasma concentration of 17.1 mcg/mL in approximately 45 minutes following a single oral dose of 1000 mg of dyphylline.
Dyphylline exerts its bronchodilatory effects directly and, unlike theophylline, is excreted unchanged by the kidneys without being metabolized by the liver. Because of this, dyphylline pharmacokinetics and plasma levels are not influenced by various factors that affect liver function and hepatic enzyme activity, such as smoking, age, or concomitant use of drugs which affect liver function.
The elimination half-life of dyphylline is approximately two hours (1.8 - 2.1 hr) and approximately 88% of a single oral dose can be recovered from the urine unchanged. The renal clearance would be correspondingly reduced in patients with impaired function. In anuric patients, the half-life may be increased to 3 to 4 times normal.
Dyphylline plasma levels are dose-related and generally predictable. The therapeutic range of plasma levels within which dyphylline can be expected to produce effective bronchodilation has not been determined.
Dyphylline plasma concentrations can be accurately determined using high pressure liquid chromatography (HPLC) or gas-liquid chromatography (GLC).
Guaifenesin is an expectorant whose action helps increase the output of then respiratory tract fluid to facilitate mucociliary clearance and removal of inspissated mucus.
Guaifenesin is an expectorant which increases respiratory tract fluid secretions and helps to loosed phlegm and bronchial secretions. By reducing the viscosity of secretions, guaifenesin increases the efficiency of the cough reflex and of cilliary action in removing accumulated secretion from the trachea and bronchi.
Guaifenesin is readily absorbed from the gastrointestinal tract and is rapidly metabolized and excreted in the urine. Guaifenesin has a plasma half-life of one hour. The major urinary metabolite is p-(2-methoxyphenoxy) lactic acid.
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