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Biomedical subjects

H Knauf

Publications and source records attributed to H Knauf.

At least 73 records · Page 4Linked to original sources
PubMed1983

[Pharmacokinetics of triamterene in healthy subjects and patients with liver and kidney function disorders].

The knowledge about the pharmacokinetics of triamterene (TA) was limited until recently. The metabolic pathway of TA is the formation of p-hydroxytriamterene (OH-TA), which is subsequently conjugated with active sulfate to form p-hydroxytriamterene sulfuric acid ester (OH-TA-ester). The phase-II-metabolite is surprisingly pharmacologically active. TA and its metabolites were measured concomitantly by a specific and sensitive tlc-method. The i.v. kinetics of TA were determined after application of a newly developed lactic acid solution of the drug. Comparing these data with results after oral application of TA the bioavailability of TA was 52% and the extent of absorption 83%. The bioavailability of different dosage forms was correlated with in vitro-tests. In liver disease the pharmacokinetics of TA are markedly altered. While in cirrhosis the hydroxylation of TA was decreased, the biliary excretion of this agent was strongly reduced in hepatitis. In renal disease the excretion of TA and OH-TA-ester was reduced proportional to the reduction of endogenous creatinine clearance. In older patients the elimination of TA was impaired.

Adult↗
PubMed1983

Pharmacokinetics of hydrochlorothiazide in relation to renal function.

The pharmacokinetics of hydrochlorothiazide (HCT) was investigated in 23 subjects with normal renal function or widely varying degrees of renal failure. The half-life of elimination increased from 6.4 h in subjects with normal renal function to 11.5 h in patients with mild renal impairment (endogenous creatinine clearance between 30 and 90 ml/min), and to 20.7 h in patients with an endogenous creatinine clearance below 30 ml/min. The cumulative urinary excretion and the renal HCT clearance were correspondingly reduced in patients with impaired kidney function. In normal subjects HCT was mainly excreted by tubular secretion, but as renal HCT clearance in patients with renal impairment did not differ significantly from endogenous creatinine clearance, it was concluded that the secretory mechanism is most markedly impaired. In patients with an endogenous creatinine clearance of 30 to 90 ml/min, the dosage of HCT should be reduced to 1/2 and in patients with a endogenous creatinine clearance below 30 ml/min to 1/4 of the normal daily dose to avoid dose dependant side-effects.

Adult↗
PubMed1983

Delayed elimination of triamterene and its active metabolite in chronic renal failure.

The kinetics of triamterene and its active phase II metabolite were studied in 32 patients with various degrees of impaired renal function; the creatinine clearances ranged from 135 to 10 ml/min. The area under the plasma concentration-time curves (AUC) for triamterene were not influenced by kidney function, but the AUCs for the effective metabolite OH-TA-ester were significantly elevated in renal failure, indicating accumulation of the metabolite. Urinary recovery of triamterene and its metabolite over a 48 h collection period was significantly reduced in renal failure. This is considered to be due to delayed urinary excretion, corresponding to reduced renal clearance. The renal clearance of the native drug exceeded that of the metabolite, because of their different protein binding, 55% for triamterene and 91% for the metabolite. The latter is eliminated almost exclusively via tubular secretion and extra-renal elimination is less important. Administration of this antikaliuretic is therefore considered hazardous in patients with impaired kidney function.

Adult↗
PubMed1983

Pharmacokinetics of triamterene.

The knowledge about the pharmacokinetics of triamterene (TA) was limited until recently. The metabolic pathway of TA is the formation of p-hydroxytriamterene (OH-TA), which is subsequently conjugated with active sulfate to form p-hydroxytriamterene sulfuric acid ester (OH-TA-ester). The phase-II-metabolite is surprisingly pharmacologically active. TA and its metabolites were measured by a specific and sensitive tlc-method concomitantly. The i.v. kinetics of TA were determined after application of a newly developed lactic acid solution of the drug. Comparing these data with results after oral application of TA the bioavailability of TA was 52% and the extent of absorption 83%. The bioavailability of different dosage forms was correlated with in vitro tests. In liver disease the pharmacokinetics of TA are markedly altered. While in cirrhosis the hydroxylation of TA was decreased, the biliary excretion of this agent was strongly reduced in hepatitis. In renal disease the excretion of TA and OH-TA-ester was reduced according to endogenous creatinine clearance. In older patients the elimination of TA was impaired.

Age Factors↗
PubMed1982

Modelling of electrolyte transport in renal and intestinal epithelia. Implications for transport defects.

Epithelia can be classified as "leaky" and "tight epithelia" due to their conductive properties and their modes of solute transport. Both the proximal segment of the nephron and the intestinal tract are "leaky" whereas the distal nephron and the colon are "tight". Consequently, inborn errors and exogenous disorders of solute transport often involve both the proximal tubule and the small intestine. In addition, effects on ion and water transport in the distal nephron closely resemble those in the large intestine. Models of solute transport in leaky and tight epithelia are presented employing porter systems known in mammalian tissues. These porter systems are discussed as possible sites of transport defects and as targets for pharmacological agents.

Amino Acid Metabolism, Inborn Errors↗
PubMed1982

Interrelationships of ion transport in rat submaxillary duct epithelium.

The transport of Na+, K+, Cl-, and HCO3(-) across the epithelium of the rat submaxillary salivary duct is postulated to be due to the coupling of the basolateral Na+-K+-ATPase with various ion transport systems in the luminal and basolateral membranes. Na+ reabsorption depends on the presence of a rheogenic (Na+ conductance) and an electroneutral (Na+:H exchange) pathway, both of which are sensitive to amiloride. K+ secretion is postulated to be mediated by a K+: H+ antiport, coupling between Na+ reabsorption and K+ secretion, thus depending on local H+ ion concentration. The ratio between electroneutral Na+ influx and K+ efflux, therefore, determines the rate of HCO3(-) secretion. In the absence of Na+ influx, although K+ efflux falls, HCO3(-) secretion rises to a value equal to that of K+ secretion. The maintenance of K+ secretion in the absence of luminal Na+ requires an additional Na+-entry step across the basolateral membrane, also postulated to be due to Na+:H+ exchange.

Animals↗
PubMed1980

[Reliable lowering of blood pressure with one tablet of Moducrin daily (author's transl)].

The effect of the combination preparation Moducrin on the blood pressure in the course of the day, the heart rate and the routine blood parameters was investigated in 25 patients with essential hypertension. The blood pressure was shown to be completely stable in the daily profile and was almost equally high in standing and supine position. The electrolyte balance remained constant in all cases. Only the serum uric acid and the creatinine rose negligibly during the treatment. The studies have shown that in 80% of patients with essential hypertension a constant lowering of blood pressure throughout the day could be achieved with one tablet of Moducrin, without upsetting the electrolyte balance.

Amiloride↗
PubMed1980

[Dose-response relationship of xipamide in healthy subjects].

To establish a dose-effect relationship for the xipamide diuretic in double-blind trials 0, 5, 10, 20 and 40 mg of xipamide were administered to 5 groups of 6 to 14 healthy test persons in each group. Before, during and after the 15-d period of application all the blood electrolytes as well as the metabolism parameters of glucose, uric acid, cholesterol, neutral fats as well as creatinine and urea were determined. Similarly during the entire period of investigation the 24-h urine samples were collected daily and from these the electrolyte excretion as well as the endogenic creatinine clearance were determined. It was found that diuresis and natriuresis significantly enhanced in comparison with placebo were already achieved with 5 mg xipamide per day, they could no further be increased by higher doses. Much rather at 40 mg xipamide per day a significant hypokalaemia as well as a light hypercalcaemia developed. Independently of the dose, during the period of investigation a light, fully compensated hypochloraemic alkalosis developed. Regarding the metabolic processes a slight increase in the uric acid and cholesterol blood levels was observed, while the blood-sugar level, the triglycerides as well as the endogenic creatinine clearance remained unaffected. It can be concluded from the investigations that maximum natriuresis and diuresis can already be achieved with a daily xipamide dose of 5 mg, while side effects can be kept at a minimum.

Adult↗
PubMed1980

[On the bioavailability of hydrochlorothiazide and triamterene from commercial drugs (author's transl)].

In a study on the bioavailability of triamterene and hydrochlorothiazide from 3 diuretics, preparation A (25 mg hydrochlorothiazide), preparation B (50 mg triamterene) and preparation C (combination of hydrochlorothiazide and triamterene), the data for tmax, Cmax, AUC and the cumulative urine excretion were determined in 7 healthy volunteers. The different formulations of the diuretics influenced the kinetics of the agents. The in vivo data agreed well with those obtained in vitro. Plasma levels of triamterene and its active metabolite from preparation C were reached more rapidly than from preparation B. However, the bioavailability of the agents was not significant different in the two diuretics when given immediately after breakfast. The AUC-data of hydrochlorothiazide determined after administration of preparation A or C do not differ significantly, only the comulative excretion of hydrochlorothiazide in urine is greater after application of preparation A than after application of preparation C.

Biological Availability↗
PubMed1980

Influence of triamterene and hydroxytriamterene sulfuric acid ester on diuresis and saluresis in rats after oral and intravenous application.

Previous transport measurements on the submaxillary duct of the rat, the model epithelium for the distal nephron, showed that even the phase-II metabolite of triamterene (TA), hydroxytriamterene sulfuric acid ester (OH-TA-ester), has a diuretic effect. The present studies were aimed at answering the question whether or not this finding was also valid in vivo. Clearance measurements in the rat after i.v. injection of OH-TA-ester did result in an increased diuresis and natriuresis. In comparison with the native triamterene the phase -II metabolite caused only a relative potassium retention. The ester was inactive when administered orally. The potassium loss after administration of furosemide could be prevented by simultaneous i.v. administration of the OH-TA-ester.

Administration, Oral↗
PubMed1980

Independent of etozolin elimination of kidney function. Single dose experiments in patients with renal insufficiency.

Following a single oral dose of the novel diuretic ethyl (Z)-(3-methyl-4-oxo-5-piperidino-thiazolidin-2-ylidene) acetate (etozolin, Elkapin), the plasma levels of the parent drug and its active metabolite (Z)-(3-methyl-4-oxo-5-piperidino-thiazolidin-2-ylidene) acetic acid (ozolinone) were determined by means of HPLC. In order to learn whether or not impairment of renal function influences the plasma levels of the diuretics and their elimination rate 19 patients with various degrees of reduced glomerular filtration rate were investigated. The lack of correlation between elimination half-life (HL) and creatinine clearance showed that there is no influence of kidney disease on the pharmacokinetic parameters of etozolin and ozolinone. Even in severe renal insufficiency the HL of etozolin and ozolinone did not differ from normal values, the mean HL of etozolin being 2.8 +/- 0.4 h and of ozolinone being 10.2 +/- 1.5 h. Also impairment of liver function did not signficantly alter the pharmacokinetic parameters of these diuretic agents. It is concluded that in the single dose experiments renal insufficiency does not significantly influence the metabolization of etozolin and ozolinone.

Adolescent↗
PubMed1979

[Lithium balance in mania].

Lithium balance studies were performed in 19 patients suffering from mania and 6 patients suffering from depression. The following results were obtained: (1) The mean daily requirement for lithium in the manic patients was 52 mM, in those with depression 30 mM (additional requirement in manic patients 73%). (2) Renal elimination of lithium, after optimal blood lithium levels had been reached, was 76% in mania and 97% in depression (retention in manic patients 21%). (3) In mania there was an unchanged lithium half-life time (12-13.5 h). (4) In mania and depression no significant differences in lithium and creatinine clearance were noted. (5) Standard diet or unrestricted sodium chloride administration did not significantly influence the lithium requirement or lithium retention. After exclusion of a renal or dietetic cause for increased lithium requirement or retention during mania, the existence of a 'lithium pool' dependent on the presence of a manic psychosis seems probable. As a result of this, somatic influences on endogenous psychosis have to be taken into account.

Adolescent↗
PubMed1978

[Distribution volume and elimination of triamterene and its active metabolites in the rabbit (author's transl)].

In rabbits the volumes of distribution of triamterene (TA) and its metabolites hydroxytriamterene (OH-TA) and hydroxytriamterene sulfuric acid ester (OH-TA-ester) were determined after i.v. administration of the agents. Both TA as well as its metabolites distribute in at least 2 compartments, OH-TA exhibiting by far the greatest volume of distribution, followed by TA and then by OH-TA-ester. TA and its phase-II-metabolite are eliminated at practically equal rate, whereas the elimination of OH-TA is relatively slow.

Animals↗
PubMed1978

[Pharmacological effects of phase-I- and phase-II-metabolites of triamterene (author's transl)].

Since triamterene (TA) is rapidly metabolized to hydroxytriamterene (OH-TA) and then to its sulfuric acid ester (OH-TA-ester) the question arose whether the metabolites are still effective on ion transport as is triamterene. The effect of the metabolites was studied in microperfusion experiments on the rat submaxillary duct, which resembles the distal nephron and is considered the site of action of triamterene. Added to the lumen the phase-I- as well as the phase-II-metabolites decreased reabsorption of Na+, secretion of K+, and yielded an accumulation of HCO3-. These effects of the metabolites were produced by equimolar concentrations and are almost identical to those of native triamterene. In conclusion, the phase-II-metabolite must be considered to be essentially responsible for the natriuresis and antikaliuresis observed after oral administration of triamterene.

Animals↗