Pharmacokinetic investigation of oral and i.v. dihydroergotamine in healthy subjects.

A new radioimmunoassay (RIA) for the specific measurement of dihydroergotamine (DHE), sufficiently sensitive for the determination of low plasma concentrations, has been used to investigate the pharmacokinetics of unchanged DHE. In a randomized cross-over trial, eight healthy male volunteers received single doses of DHE 5 mg, 10 mg and 20 mg orally and 0.1 mg and 0.

Steady state pharmacokinetics of hydrolysed bopindolol in young and elderly men.

Steady-state pharmacokinetic parameters of the new, long-acting beta-adrenoceptor blocker bopindolol have been measured in 17 young and 20 elderly healthy men. The t 1/2 beta and the AUC(0----24 h) of hydrolysed bopindolol (the active metabolite) were both increased (40% and 26%, respectively) in the elderly subjects but tmax, Cmax and CL/f were not altered. However, after adjusting the parameters to allow for the different average body weights of the two groups, Cmax and CL/f became significantly different (+29% and -30%, respectively).

Sandostatin, a new analogue of somatostatin, reduces the metabolic changes induced by the nocturnal interruption of continuous subcutaneous insulin infusion in type 1 (insulin-dependent) diabetic patients.

With the aim of assessing a new somatostatin analogue to prevent the metabolic changes induced by a 6-h nocturnal arrest of an insulin pump, nine C-peptide negative Type 1 (insulin-dependent) diabetic patients were submitted blindly to two interruptions (from 23.00 to 05.00 hours) of their continuous s.

Monoclonal antibodies for radioimmunoassay of cyclosporine: a multicenter comparison of their performance with the Sandoz polyclonal radioimmunoassay kit.

The performance of a radioimmunoassay kit containing monoclonal specific and nonspecific antibodies to cyclosporine (Sandimmun-Kit; Sandoz Ltd., Basle, Switzerland) was compared with that of the original Sandoz polyclonal radioimmunoassay kit (Ciclosporin RIA-Kit). A total of 1320 blood and plasma samples from patients receiving cyclosporine after kidney, heart, liver, and bone-marrow transplantation were analyzed at six centers.

Specific 3H radioimmunoassay with a monoclonal antibody for monitoring cyclosporine in blood.

A specific radioimmunoassay involving a mouse monoclonal antibody to cyclosporine has been developed for monitoring the parent drug in blood. Pretreatment with methanol removes cyclosporine from the erythrocytes. The limit of detection is about 12 micrograms/L, sample volume is 50 microL of blood, and within- and between-assay CVs are less than 7%.

A new radioimmunoassay of thioridazine and its comparison with a high performance liquid chromatographic method and another radioimmunoassay.

A new radioimmunoassay (RIA) procedure for the determination of thioridazine in plasma is described. Antiserum was produced in rabbits immunized with N-(2-carboxyethyl)desmethylthioridazine-protein conjugate. The developed RIA procedure can measure as low as 80 pg of thioridazine in a 200-microliter human plasma sample with a coefficient of variation of less than 5%.

Dihydroergotamine: pharmacokinetics, pharmacodynamics, and mechanism of venoconstrictor action in beagle dogs.

Dihydroergotamine (DHE) elicits selective and long-lasting venoconstrictor activity, although the drug disappears rapidly from the blood. Therefore, a comparative study on the pharmacokinetic and pharmacodynamic properties of DHE was performed in beagle dogs. In addition, the mechanism of the venoconstrictor activity of DHE was investigated in vivo.

Description of the time course of the prolactin suppressant effect of the dopamine agonist CQP201-403 by an integrated pharmacokinetic-pharmacodynamic model.

Six male volunteers (mean age 24 years) received a single oral dose of 0.025 mg CQP201-403 and placebo in a randomised double-blind crossover design. Fifteen plasma samples were collected over 48 h and were assayed by radioimmunoassay for drug substance and prolactin (PRL).

Pharmacokinetics of a long-acting bromocriptine preparation (Parlodel LA) and its effect on release of prolactin and growth hormone.

The pharmacokinetics and endocrine actions of a long-acting form of bromocriptine (Parlodel) were examined in a controlled study in 10 healthy volunteers receiving a single i.m. injection of 50 mg.

Venoconstrictor effects of dihydroergotamine after intranasal and intramuscular administration.

A parenteral formulation of dihydroergotamine (DHE) is the only galenical form now available for the treatment of acute attacks of migraine in which a rapid onset of action is required. A recently developed nasal spray of DHE has been compared with intramuscular DHE for its venoconstrictor activity. In a randomised double-blind, cross-over trial, 9 healthy male volunteers received a single dose of DHE 1 mg intranasally, DHE 0.

Pharmacokinetics of SMS 201-995 in healthy subjects.

The pharmacokinetics of a new somatostatin derivative, SMS 201-995, was investigated in a group of eight healthy subjects. SMS 201-995 was given intravenously in doses of 25 micrograms, 50 micrograms, 100 micrograms, and 200 micrograms and also subcutaneously in doses of 50 micrograms, 100 micrograms, 200 micrograms, and 400 micrograms in accordance with a randomized Latin-square design. Blood samples were taken up to 8 h.

Relationship between plasma concentrations and cardiac beta-adrenoceptor blockade--a study with oral and intravenous bopindolol.

Bopindolol, an esterified beta-adrenoceptor blocking drug, was administered to nine healthy male volunteers in oral (1 mg and 4 mg) and intravenous (1 mg) doses. Plasma concentrations determined using a radio-receptor assay (RRA) and high pressure liquid chromatography (h.p.

Interindividual variation of beta-adrenoceptor blocking drugs, plasma concentration and effect: influence of genetic status on behaviour of atenolol, bopindolol and metoprolol.

Ten healthy subjects whose genetic oxidative phenotype had been determined (6 extensive and 4 poor metabolizers of the debrisoquine-sparteine type of polymorphism) received single oral doses of 3 beta-blockers: atenolol, bopindolol and metoprolol. The plasma concentrations and the extent of the decrease in exercise-induced tachycardia were determined. The oxidative polymorphism was only significant for substances that had a high hepatic first pass metabolism, such as metoprolol.

Simultaneous modeling of bopindolol kinetics and dynamics.

Bopindolol has beta-blocking effects for 96 hr despite a 4-hr t1/2. To investigate the concentration-effect relationship after single and repeated doses. 2-mg oral doses were given once and then daily for 13 days to six healthy subjects.

Immunoassay of ergotamine and dihydroergotamine using a common 3H-labelled ligand as tracer for specific antibody and means to overcome experienced pitfalls.

A highly sensitive radioimmunoassay for the determination of ergotamine and dihydroergotamine is described. The limit of detection is about 9 pg/mL blood plasma for both compounds. The specificity of the gamma-globulin, which was prepared from rabbit antiserum, was investigated in the presence of compounds synthesized as possible metabolites.

Ex vivo studies after oral treatment of the beagle with dihydroergotamine.

Plasma concentrations of unchanged dihydroergotamine (DHE) were measured in beagle dogs on days 1 and 7 of a 1 week treatment with daily oral doses of DHE. Responses to both 5-HT and noradrenaline were monitored isometrically on spiral strips from saphenous arteries and femoral veins removed 24 and 72 h after the last oral dosage of DHE. Femoral vein strips were removed from dogs treated for 1 week with daily doses of 0.

Ergotamine in plasma and CSF after i.m. and rectal administration to humans.

An attempt was made to study the kinetics of penetration of ergotamine across the blood-brain barrier. A single therapeutic dose of ergotamine was given to 18 hospitalized patients; eight patients received 0.5 mg i.

The role of D-1 and D-2 receptors.

Dopamine receptors in intracerebral motor and endocrine systems have been divided into two main types, D-1 and D-2, dependent on the presence or absence of adenylate cyclase linkage. Here we have investigated a number of dopamine agonist and antagonist drugs in man that have different actions on D-1 and D-2 receptors in animals. Motor and endocrine effects in parkinsonian subjects seem to depend on drug interaction with D-2, but not D-1, receptors.

Dependence of area under the curve on proquazone particle size and in vitro dissolution rate.

The in vitro dissolution and GI absorption of various sieve fractions of proquazone were studied (particle-size ranges of 45-74, 160-300, and 500-1000 micrometer). The dissolution rates of preparations F45, F160, and F500 were determined in vitro in a flow-through assembly in artificial gastric juice at 37 degrees. The time required for 63% of the maximum amount of soluble drug to pass into solution was characterized by the dissolution variable tau D.

Plasma bromocriptine levels, clinical and growth hormone responses in Parkinsonism.

1. Plasma bromocriptine levels following separate oral doses of bromocriptine 12.5, 25, 50 and 100 mg have been determined in ten subjects with parkinsonism.

Non-equilibrium method for the radioimmunoassay of clozapine in the presence of metabolites.

Cross-reactions with metabolites are an ever-recurring problem encountered in the use of radioimmunoassay techniques to determine active compounds in biological material. Metabolites may interfere with the assay of the parent drug to a variable extent. Taking 8-chloro-11-(4-methyl-1-piperazinyl)-5H-dibenzo[b,e][1,4]diazepine (clozapine as an example, it was shown that the extent to which the antiserum produced interacts with the parent drug and the metabolites can be estimated by determining the equilibrium constants and the kinetics.