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Biomedical subjects

I Shudo

Publications and source records attributed to I Shudo.

13 recordsLinked to original sources
PubMed1979

Pharmacokinetics of verapamil in man.

Verapamil was given intravenously (10 mg) and orally (120 mg) in six healthy subjects. After intravenous administration, the serum levels in all subjects declined bi-exponentially. Thereupon, pharmacokinetic parameters were calculated using a two-compartment open model. The half-lives of distribution (T 1/2 alpha) and elimination (T 1/2 beta) phases showed 0.23 hour and 4.21 hour on an average respectively. The apparent volume of distribution [Vd (area)] showed 2.51 1/kg and body clearance (C1b) showed 500.64 ml/min on an average. Renal clearance was smaller than normal human creatinine clearance. After oral administration, the time to reach peak blood level (Tmax) was reached within 1.84 hour and the peak serum concentration showed 219.09 ng/ml on an average. The bioavailability was only 22.47% on an average. Verapamil produced a marked prolongation of PQ interval on electrocardiogram and the degree of PQ interval prolongation was closely related to the increase in serum concentration of this compound. QRS, QTc and RR interval were not changed by this compound.

Administration, Oral↗
PubMed1975

The modification of inotropic action of ouabain by 6-hydroxydopamine and alpha-methyl-p-tyrosine in dogs.

The action of ouabain on myocardial inotropism pretreated with 6-hydroxydopamine and alpha-methyl-p-tyrosine was studied. Inotropic action of ouabain was not changed by depletion of catecholamines in the brain, in which the central sympathetic neurons were destroyed by an intraventricular administration of 6-hydroxydopamine. Systemic administration of 6-hydroxydopamine and alpha-methyl-p-tyrosine reduced ventricular catecholamines to 5.3% and 20.8% of the control, respectively. Percent increase of contractility by ouabain after the pretreatment of 6-hydroxydopamine and alpha-methyl-p-tyrosine was reduced to 16.7% and 50.3% of the control, respectively. The results obtained suggest that catecholamines in the myocardium play some important role in producing cardiotonic action of cardiac glycosides. Brain catecholamines or the central sympathetic nervous system do not appear to participate in the exertion of the positive inotropic action of cardiac glycosides.

Animals↗
PubMed1975

On the diuretic action produced dibutyryl cyclic AMP in dogs.

Experiments were undertaken on order to elucidate the mechanism of diuresis induced by dibutyryl cyclic AMP in dogs. Intravenous injections of dibutyryl cyclic AMP produced an increase in urine flow in dogs hydrated with saline. It was also noted that dibutyryl cyclic AMP produced an increase in myocardial contraction, renal blood flow and glomerular filtration rate; In addition, unilateral injection of dibutyryl cyclic AMP into the left renal artery produced diuresis bilaterally. Based on the above findings it was suggested that the diuretic action induced by dibutyryl cyclic AMP is associated with its hemodynamic effect.

Animals↗
PubMedDate not supplied

Disposition kinetics of disopyramide in patients with renal insufficiency.

The pharmacokinetics of an intravenous injection of disopyramide was studied in five normal subjects and six patients with varying degrees of renal impairment. The elimination rate constant (beta) was related to the endogenous creatinine clearance (Clcr). However, a decrease in beta was not observed until the Clcr was reduced below 40 ml min-1. Below 40 ml min-1 a linear relationship existed between beta and Clcr. Similarly, the plasma elimination half-life (t 1/2 beta) showed a significant increase when the Clcr was less than 30 ml min-1. Hence, dosage modification for disopyramide is necessary only when renal function is severely impaired. Overall, the apparent volume of distribution in patients with renal insufficiency was reduced to two-thirds of that in normal subjects. Therefore, in patients with Clcr less than 40 ml min-1 both the loading and maintenance dose of disopyramide should be reduced.

Arrhythmias, Cardiac↗
PubMedDate not supplied

The effects of urine pH and plasma protein binding on the renal clearance of disopyramide.

To ascertain whether the renal clearance of disopyramide (pKa = 8.36) is affected by urine pH, the disposition kinetics of disopyramide were compared during excretion of acidic and alkaline urine following both single dose intravenous (2mg/kg) and oral (5 mg/kg) administration to 4 healthy male volunteers. No significant difference was observed in the plasma concentration-time curve of disopyramide. The mean 72 hour recovery of disopyramide and its N-deisopropyl metabolite (MND) in urine was 55.1 and 20.3% of the dose respectively, with no apparent difference between the two routes of administration or pH of urine. Renal clearance of disopyramide was found to vary with time, which is partly the result of a concentration dependent change in plasma protein binding. The unbound fraction of drug in plasma varied from 0.32 to 0.72 between 0.4 to 4microgram/ml concentration. However, time-dependent change in renal clearance of disopyramide persists even after correction for plasma protein binding.

Administration, Oral↗