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Biomedical subjects

P Müller-Seydlitz

Publications and source records attributed to P Müller-Seydlitz.

12 recordsLinked to original sources
PubMed1979

Alterations in the disposition of differently cleared drugs in patients with cirrhosis.

We have compared the disposition of antipyrine orally (15 mg/kg) and the new antiarrhythmic drug lorcainide intravenously (1.5 mg/kg) in 8 patients with alcoholic cirrhosis. Antipyrine (AP) serves as a model drug for drugs which are eliminated independently of liver blood flow and lorcainide (L) elimination as a model for drugs which depend on liver blood flow. Since in healthy subjects elimination half-life (t 1/2) of L increased with age (r = 0.68, p less than 0.01) due to parallel change in the volume of distribution (r = 0.52, p less than 0.05), its disposition had to be compared to age-matched controls. Elimination of both AP and L was impaired in cirrhotic patients, expressed either in terms (mean +/- SD) of t 1/2 (AP = 26.8 +/- 15.0 hr and 12.3 +/- 1.8; L = 12.5 +/- 4.5 hr and 7.7 +/- 2.2 hr, p = 0.002) or of clearance (Cl) (AP = 21.9 +/- 7.9 ml/min and 41.7 +/- 5.5 ml/min; L = 814 +/- 144 and 1002 +/- 304 ml/min, p = 0.06). While the alterations in plasma Cl were great for AP, they were smaller for L. This suggests that elimination of drugs in cirrhotic patients is associated with relatively more impairment of enzyme activity than of hepatic blood flow. The slightly decreased Cl of L in patients with alcoholic cirrhosis would suggest that L should be carefully handled in patients with dysfunction of the liver.

Acetanilides↗
PubMed1979

Disposition and antiarrhythmic effect of lorcainide.

The disposition and the antiarrhythmic effect of lorcainide (R 15,889) were investigated in 11 patients with ventricular premature beats (VPB) after a single intravenous dose of 100 mg or 2 mg/kg and after multiple intravenous and oral dosing. Pharmacokinetic parameters were computed according to the two-compartment open model. The half-life of the initial phase, t 1/2 (alpha), was calculated as 0.3 +/- 0.1 hr (mean +/- SD) and the terminal half-life, t 1/2 (beta), varied independently of the dose and route of administration between 5.8 and 12.5 hr (7.8 +/- 2.5 hr). After the single intravenous dose total plasma clearance (Cl) ranged from 570 to 1670 ml/min (988 +/- 425 ml/min) while after multiple dosing Cl decreased to 666 +/- 27 ml/min. Comparison of the area under the curves during steady state (ss) indicated a complete bioavailability of multiple oral doses. After the single intravenous dose, VPB were diminished or reduced for about 4 hr if the plasma concentrations exceeded 120 to 150 ng/ml. During ss-therapy plasma levels fluctuated between 200 and 550 ng/ml with an effective prevention of arrhythmias. Thus, the new drug demonstrates a therapeutic range of approximately 150 to 400 ng/ml and oral therapy seems to be effective with 100 mg t. i. d.

Acetanilides↗
PubMed1975

[Valvular replacement in florid endocarditis. Report on 5 cases].

This is an account of experience with valve replacement in patients with active endocarditis. In four patients the aortic valve was replaced, and in one, the mitral valve. Indication for surgery in all five cases was heart insufficiency. Two patients died, one of acute left heart failure five weeks postoperatively, and one of brain embolus in the presence of persisting acute endocarditis, four months postoperatively. Covered in the discussion are other indications for valve replacement in the presence of acute endocarditis, namely, serial emboli, fungus endocarditis, resistance to and toxic reactions of antibiotics, and mycotic sinus of valsava aneurysm. In conclusion, results obtained by other authors are reported.

Acute Disease↗
PubMed1975

[The fate of the pulmonary hypertension after ASD-closure in adults (author's transl)].

10 female and 7 male patients, who were operated for secundum type Atrial Septal Defect with Pulmonary Hypertension, got postoperative check-ups including right heart catheterisations. The investigations were performed on the average 6.6 years postoperatively. There was a fall of the systolic pulmonary pressure and of the flow; pulmonary resistance fell in 8 cases and rose in 9. The low left ventricular cardiac index together with an elevated left atrial pressure may be the pathogenetic cause of postoperatively elevated pulmonary resistance.

Adolescent↗
PubMedDate not supplied

Pharmacokinetics of lorcainide in man: a new antiarrhythmic agent.

A gas liquid chromatographic assay was developed to measure in plasma and urine concentrations of the new antiarrhythmic drug lorcainide, its dealkylated metabolite and an added internal standard of similar structure. The limit of sensitivity was 10ng/ml plasma. In 5 healthy volunteers and in 6 patients with ventricular premature beats (VPB) the pharmacokinetics were determined after a single intravenous dose of 100mg. In 4 of the patients with VPB, the disposition was also evaluated under steady-state conditions following oral administration of 100mg twice daily. In 4 of the healthy volunteers, the bioavailability of a single 100mg(n = 2) and 150mg (n = 2) oral dose was determined. In an additional crossover experiment, bioavailability of a single oral dose of 100 and 200mg was also measured in 2 patients with VPB. Less than 2% of the intravenous dose could be recovered as unchanged lorcainide in the urine, indicating extensive metabolism. The drug was bound to plasma proteins to the extent of 85.0 +/- 5.0% (mean +/- SD) in healthy subjects and 83.3 +/- 2.9% in patients with VPB. Since the plasma levels declined biexponentially after an intravenous dose, data were analysed according to a 2-compartment open model. The elimination half-life (t1/2beta) of 5.1 +/- 0.6h (healthy subjects) was somewhat longer (p = 0.02) in patients with VPB (7.6 +/- 2.2h), but total plasma or blood clearance were very similar; the latter approaching a normal liver blood flow of 1.5L/min. The apparent distribution volumes Vdbeta (8.6 +/- 2.4L/kg vs 10.7 +/- 4.2L/kg) and Vdss (6.4 +/- 2.4L/kg vs 8.8 +/- 3.4L/kg) showed no statistically significant difference between the healthy subjects and patients. After oral doses, high and saturable first--pass hepatic metabolism seems to exist. The crossover experiments in 4 subjects indicated bioavailability of about 1 to 4.5% after a single 100mg dose, between 7 and 20% after a 150mg dose, and between 35 and 65% after a 200mg dose. In contrast, 3 of 4 patients with VPB on oral maintenance therapy exhibited bioavailability of 100%. This indicates that lorcainide belongs to the group of drugs exhibiting non-linear elimination kinetics.

Acetamides↗