The present study was undertaken to elucidate the pharmacokinetics of procainamide (PA) in 4 Japanese who were found to be so-called fast acetylators. PAwas injected intravenously and the serum concentrations of PA and N-acteylprocainamide (NAPA) were determined, following which the pharmacokinetic parametersof PA were calculated. In this study, it was found that the elimination rateconstant (k_μ) ranged from 0.22 to 0.43hr^-1, the apparent volume of distribution (Vdarea) ranged from 1.80 to 3.57 1/kg, body clearance (Cl_b) ranged from 0.65 to 1.39l/kg/hr, and the area under the curve (AUC) ranged from 2.99 to 5.22 μg/hr/ml.Even after repeated oral administration to Japanese subjects, the serum concentration of PA did not reach the therapeutic range recommended by previousworkers, while on the other hand, a remarkable increase in serum concentrationof NAPA accompanied by the equilibrium state of serum PA concentration wasnoted. From the present results, it was suggested that the serum concentrations ofboth PA and NAPA should be taken into consideration in order to evaluate theantiarrhythmic effect after PA administration to Japanese subjects, most ofwhom are fast acetylators.

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The clinical significance of drug interactions was studied in a 1052-bed university teaching hospital using a retrospective method. Seven DIAL (Drug Interaction Alert List) drugs, including digitalis, gentamicin, tetracyclines, phenylbutazone, guanethidine, and anabolic steroids, were selected for study. The medication orders of all patients were screened for one month to determine the incidence of potentially interacting drug combinations. The charts of patients towhom these combinations were prescribed were searched for signs of drug interactions.
The incidence of potentially interacting drug combinations with digitalis andgentamicin was high, but with others very low. Twenty-five out of 58 patientsstudied had some sorts of adverse drug reactions which could be possibly due todrug interacions. However, after analysing each patients, we came to the conclusion that 5 were probable, six possible, and 14 non-drug interactions. Theprobable adverse drug interactions occurred as ; 5%, digitalis-potassium-losingdiuretics ; 5.6%, gentamicin-cephalosporines; 67%, warfarin-phenytoin ; and 33%, warfarin-phenobarbital combinations. But most of these interactions seem ofminor significance clinically.

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The concentrations of cinepazide in human plasma and urine were studied byusing high-performance liquid chromatography. Each of 7 healthy, male volunteersreceived 200 and 400 mg of cinepazide on separate occasions for single doseexperiments. In the case of the 200 mg single dose, a rapid peak of plasma concentrationat2.8-4.9μg/ml was observedat 1-3hr, and 57.6% of the cinepazidewas excreted in urine within 24 hr. The peak plasma level increased proportionallywith the dose of cinepazide, whereas the extent of cinepazide excretionincreased slightly with the dose.
In multiple dose experiments, each of these volunteers received, on two separateoccasions, 200 mg of cinepazide t. i. d. at 9: 00 am, 1: 00 pm and 5: 00 pm eachday for 1 day and 5 days, respectively. The results on the peak and valley plasmalevels of multiple dose cinepazide indicated reproducible absorption in comparisonwith values predicted using a computer program describing a one compartment, open pharmacokinetic model. The extent of cumulative urinary excretion ofcinepazide was nearly constant during multiple dose experiments . No side effectswere noted.

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The new β-blocker penbutolol's clinical efficacy on ventricular extrasystoleswas studied by a double-blind test using a placebo as control .
Penbutolol at 20mg/day was administered divided into 2 daily doses. As adouble cross-over method alternating penbutolol with placebo at one-week intervals was adopted, the test period was 3 weeks.
The analysis of variance revealed that penbutolol was superior to placebo in the ECG evaluation of efficacy on extrasystoles, in the degree of improvement of thesymptoms, and in the comprehensive judgement of efficacy.
There was no difference in the total number of side effects between penbutololand placebo. Abnormalities of s-GOT, s-GPT and leukocyte count were observedin some cases.
The effect of penbutolol on blood pressure and heart rate was also studied.

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The pharmacokinetics, pharmacodynamics and safety of thymoxamine were studied in 3 healthy male subjects by intravenous injection of thymoxamine hy drochloride at doses of 2, 5 and 10mg. Each subject recieved one dose at each level, the amount increasing with each week's injection.
Each subject rested in supine position on the examination bed while the fol lowing parameters were continuously monitored for 2-3 hours: systolic blood pressure ; deep body temperature at the forehead, palm and sole ; fingertip skin temperature ; blood flow in the skin at the wrist ; ECG ; and respiratory rate.
Thymoxamine tended to lower the blood pressure and elevate the peripheral temperature. Some subjects had a warm feeling at the extremities and flushed feeling at the cheeks.
The ECG and the respiratory rate showed no significant change. The half time of this drug was found to be 83 min. The urinary excretion rate was 20.3% within 24 hours. The feces excretion rate was 2.0% within 72 hours. No side effect noted in laboratory tests were observed during this study.

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This study was designed to evaluate the effect of methylcobalamin on the myelinated fiber degeneration produced by acrylamide intoxication in rats. Twelve Sprague-Dawley rats were fed a stock diet with water containing 500ppm acrylamide ad libitum for three weeks. During additional three weeks, the acryl amide was withdrawn.
Methylcobalamin, 500μg/kg, was intramuscularly administered to 6 rats as the test and 0.675% NaCl solution was intramuscularly administered to 6 rats as the control for the period of 6 weeks. All rats developed a waddling and paretic gait after twelve days of intoxication. In the control, two rats died on the 19 th and 20th days of intoxication, respectively. No rats died in the test. Three test and two control rats were sacrificed at a time, and both the sural and the peroneal nerves harvested were processed for morphometric studies at the end of the 3rd and 6th weeks of the experiment.
In teased fiber analysis the frequency of axonal degeneration of myelinatedfibers was lower in tests than in control rats for each of four different nerves (the proximal, at midthigh, and distal, at ankle, sural nerves and proximal, at mid thigh, and distal, at knee, peroneal nerves). It was significantly lower in test than in control rats (p<0.02) in the combined test of the four different nerves. Although the density of myelinated fibers was higher in test than in control rats, the difference between the test and control rats was not significant. The total number of myelinated fibers in test rats was significantly greater than in control rats for both proximal and distal sural nerves (p<0.05 and p<0.01).
The data suggested that methylcobalamin may have played a protective role against the axonal degeneration and subsequent loss of myelinated fibers in acrylamide neuropathy of rats.

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Nicotine levels in four cigarette smoking rhesus monkeys were measured by gas-liquid chromatography and compared with levels similarly obtained for two human smokers.
A range of 18.9-39.1 ng/ml was achieved by the monkeys during smoking, highter than that of the human smokers after smoking a cigarette.

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