Determination of short-term myocardial drug uptake and subsequent redistribution was performed in 27 patients with ischemic heart disease for the antiarrhythmic agents lidocaine and mexiletine, using frequent simultaneous measurements of drug concentration in aortic and coronary sinus blood, combined with measurement of coronary sinus blood flow after intravenous bolus injection of the drug. Maximal myocardial drug content per unit resting coronary sinus blood flow (MDC:F) was significantly greater in patients in whom coronary sinus pacing at 100 beat/min was performed during the initial period of drug uptake. Maximal myocardial drug content occurred after 2.4 + 0.2 (SEM) for lidocaine and after 5.5 ± 0.6 min for mexiletine (p < .001), and pacing did not affect time to maximum myocardial drug content. In nonpaced, but not paced, patients maximal MDC:F was greater in the lidocaine group than that in the mexiletine group. The subsequent efflux of lidocaine from the myocardium was more rapid that that of mexiletine in both paced and nonpaced groups. Circulation 73, No. 5, 987-996, 1986 able has been derived from conventional pharmacokinetic studies, which use peripheral venous blood sampling to examine the clearance of drugs from blood or plasma1-3 and rely on the assumption that drug uptake into the myocardium is a component of "central compartment" kinetics.' However, short-term studies correlating electrophysiologic effects of drugs such as procainamide5 and verapamil6 with plasma drug concentrations have served to emphasize the lack of equilibrium between plasma and myocardium under non--steady-state conditions and have raised the possiblity that at least part of the myocardium acts as a "peripheral" compartment of drug uptake despite relatively high global perfusion.7We now report the development of a method for the determination of short-term drug uptake in man and of the subsequent pattern of drug efflux from the myocardium. This method has been applied initially to the type IB antiarrhythmic agent lidocaine and to its derivative mexiletine, and offers a potential means of correlating myocardial drug content, drug effects, and the results of conventional pharmacokinetic studies. MethodsPatients

Lactate dehydrogenase from Streptococcus cremoris US3, which has a molecular weight in solution of 140000, was found by dodecylsulphate‐gel electrophoresis to have a minimum molecular weight of 37000. It is, therefore, a tetramer. Approximately 40 tryptic peptides were obtained by fingerprinting and in conjunction with the amino acid composition this indicates that the subunits are similar and probably identical. There is one thiol group per subunit. p‐Chloromercuribenzoate inhibits the enzyme.

A method for measuring plasma prazosin concentrations is reported. This method, which involves high pressure liquid chromatography (HPLC) combined with fluorescence detection, has a sensitivity 20 times that of previous conventional fluorimetric techniques and twice that of other HPLC methods, and can be used to study the pharmacokinetics of prazosin at very low doses. Plasma prazosin concentrations were measured in 5 normal volunteers for 24 hours after single oral doses of 0.5 and 1.5mg of prazosin. On average, the lag time was 0.650 and 0.448 hours, and the elimination half-life 2.3 and 2.5 hours, for the 0.5 and 1.5mg doses, respectively. Peak prazosin concentrations occurred between 1.1 and 3.6 hours after dosing, and after the 1.5mg doses were associated with symptoms of faintness.

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