Pharmacokinetics of falipamil after intravenous administration to humans.

Falipamil (2-[3-[3-(3,4-dimethoxyphenetylmethylamino]propyl]-5,6- dimethoxyphthalamidine; 1) is a new specific bradycardic agent for the treatment of sinus tachycardia. Pharmacokinetics of falipamil in humans (n = 6) was determined in plasma and urine after iv administration of 100 mg (1.85 MBq) per person of 14C-labeled drug by liquid scintillation counting and by a specific, sensitive reversed-phase totally automated HPLC system with fluorimetric detection.

[The pharmacokinetic and toxicologic profile of 8-methoxypsoralen. The basis for safe and effective PUVA therapy].

On the basis of approximately 60 publications and in view of our own results we present a comprehensive review as to the mode of action, the pharmacokinetics, the metabolism and the toxicology of 8-methoxypsoralen (8-MOP) and its consequences in the PUVA therapy of psoriasis. The interaction of 8-MOP with DNA is presently considered to be the most likely mode of action. 8-MOP is subject to strong first-pass effects with considerable individual variations in plasma levels.

Kinetic and analytic investigations on the formation of N-nitroso-N-methyl-N-cyclohexylamine from bromhexine and nitrite.

Bromhexine (N-methyl-N-cyclohexyl-(2-amino-3,5-dibromobenzyl)-ammoniumhydr ochloride) forms N-nitroso-N-methyl-N-cyclohexylamine (NMCA) under the conditions of the WHO Nitrosation Assay Procedure (NAP-test). The formation kinetics of this compound was investigated. The formation of NMCA depends on the square of the nitrite concentration.

Lack of detectable N-nitroso-N-methyl-N-cyclohexylamine in humans after administration of bromhexine.

The possible formation of N-nitroso-N-methyl-N-cyclohexylamine (NMCA) from the drug bromhexine (N-methyl-N-cyclohexyl-(2-amino-3,5-dibromobenzyl)-ammonium hydrochloride) and nitrite was investigated in humans using three different approaches: 1. analysis on metabolites of NMCA in human urine; 2. analysis on NMCA in human gastric juice; 3.

Pharmacokinetics and pharmacodynamics of psoralens after oral administration: considerations and conclusions.

We discovered a strong but saturable first-pass effect after oral administration of psoralens by using different doses and simultaneous or timed application of stable isotopes. Therefore, small variations of dose, disintegration of drug, and amount and rate of absorption gave rise to great differences in plasma levels and therapeutic efficacy. For practical therapy, the following conclusions can be drawn: 1) Galenical forms of psoralens should ensure a quick and highly reproducible absorption.

Clinical pharmacology of oral psoralen drugs.

Proper oral PUVA therapy includes the application of a psoralen drug and the administration of light, and both of these have to be adjusted to each other in regard to dose and timing. As psoralens are rather insoluble, it is difficult to produce pharmaceutical formulations which ensure safe and predictable absorption. A strong, saturable first pass effect occurs after oral intake of psoralens, resulting in a wide variability in plasma levels and thus also in phototoxicity.

Assay of bromhexine in human plasma by capillary gas--liquid chromatography with nitrogen-selective detection and selected ion monitoring.

A specific, sensitive method for the determination of bromhexine in human plasma is described. It comprises a selective extraction procedure and a specific determination with capillary gas--liquid chromatography and nitrogen-selective flame ionization detection. The detection limit of the assay is about 0.

Fully automated high-performance liquid chromatography. A new chromatograph for pharmacokinetic drug monitoring by direct injection of body fluids.

A new fully automated high-performance liquid chromatography is described which detects drugs from directly injected plasma (urine, saliva) without sample pretreatment. The apparatus consists of a programmable automatic sampling unit, which is connected via two alternating working pre-columns to an analytical column ("alternating pre-column sample enrichment"). The new device is able to operate with directly injected body fluids like an auto-analyzer and is especially useful for pharmacokinetic and clinical studies, where drug concentrations have to be determined from plasma, urine or saliva.

Pharmacokinetics of oxazepam following multiple administration in volunteers and patients with chronic renal disease.

The plasma level course and the elimination of oxazepam (Adumbran) via urine were investigated following multiple oral administration in volunteers and patients with chronic renal failure. Additionally, drug metabolizing enzyme systems had been induced in the volunteers by pretreatment with phenobarbital. The plasma protein binding in vitro of oxazepam was determined in volunteers and patients.

The use of stable isotopes to prove the saturable first-pass effect of methoxsalen.

Methoxsalen, administered orally shows a strong, albeit saturable first-pass effect, as demonstrated by classical dose linearity testing and by a new method, using stable isotopes and gas chromatographic mass spectrometric analysis. The therapeutic consequences of the first-pass effect are discussed.

The metabolism of 8-methoxypsoralen in man.

8-Methoxypsoralen is metabolized rapidly and completely in man. Most of the metabolites presently known have their origin in a metabolic attack on the furan moiety yielding an aryl-diol and aryl-acetic-acid and are excreted as conjugates.

[A sensitive, specific colorimetric method for determining paracetamol in human plasma (author's transl)].

A sensitive and specific colorimetric assay for paracetamol (acetaminophen) in plasma is described. After a selective column extraction (Extrelut) and hydrolysis, paracetamol is determined by the (modified) Axelrod and Brodie procedure. The whole processing is performed in a centrifuge tube.

The pharmacokinetic profile of pirenzepine.

This paper gives a brief review of the pharmacokinetic studies performed on pirenzepine (L S 519 Cl2, Gastrozepin hitherto. Particular attention will be paid thereby to the clinical significance of the pharmacokinetic parameters.

Pharmacokinetics and metabolite-pattern of 8-methoxypsoralen in man following oral administration as compared to the pharmacokinetics in rat and dog.

Following oral administration of 14C labelled 8-methoxypsoralen (8-MOP) in man the plasma level course, the metabolite-patterns and the elimination of the parent compound and its metabolites have been investigated. Additionally the results discovered have been compared with the data of pharmacokinetics on dog and rat. In man and rat the plasma protein binding of 8-MOP has been determined.

[Ambroxol, studies of biotransformation in man and determination in biological samples (author's transl)].

15 mg trans-4-[2-amino-3,5-dibromo-benzyl)-amino]-cyclohexanol-hydrochloride (ambroxol, NA 872) was administered i.v. and orally to healthy volunteers.

[Ambroxol, comparative studies of pharmacokinetics and biotransformation in rat, rabbit, dog and man (author's transl)].

Pharmacokinetics and biotransformation of trans-4-(2-amino-3,5-dibromo-benzylamino)cyclohexanol hydrochloride (ambroxol, NA 872 Cl) was studied using the 14C-labelled compound. Absorption after oral administration was found to be fast and complete. Elimination half-life of radioactivity in the blood was estimated as 20--25 h in rat, dog and man and as 2 h only in rabbit.

[Alterations in pharmacokinetics during toxicity tests (author's transl)].

Some possible reasons are discussed which may lead to changes in the pharmacokinetics of a drug during long-term toxicity tests. Since most of these alterations have toxicological consequences, their evaluation can be helpful in the interpretation of toxicity studies. Furthermore, and altered pharmacokinetic profile may be a diagnostic tool for the detection of organ damage (e.

[Model building in pharmacokinetics/Part V: Simulation of blood level curves following repetitive dosing and their experimental verification (author's transl)].

An equation is given to describe the plasma level curve of any linear compartment model following multiple dosing of various doses after various time intervals. The equation is especially suitable to be used with desk top computers equipped with a plotting device. A dosage regimen can be simulated using the parameters derived from single dose experiments.

[Model building in pharmacokinetics/Part III: Simplified rules for the deduction of analytical solutions for linear compartment models (author's transl)].

Analytical solutions for any linear compartment model are obtained empirically by use of simple rules. Set up of differential equations and tedious integration procedures are thus avoided. The procedure is suited for automation by a calculator.

[Model building in pharmacokinetics/Part II: Generalized theoretical presentation of complete integration of linear compartment models of optional structure (author's transl)].

The method of Laplace transformation is used to obtain the integral of linear differential equations for pharmacokinetic models. A general solution uniform in structure for all types of models (mammillary, catenary, mixed) was established. Choice of one more application compartments, of kinetics describing the input procedure and of elimination pathways is free.