Rapid achievement of a serum concentration plateau of digoxin through controlled infusion

Weiß, Michael; Sziegoleit, W; Fahr, A; Förster, W

doi:10.1007/bf00542110

Cited by 8 publications

(3 citation statements)

References 10 publications

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“…A human dose prediction for BKIDC-1553 was generated using estimated human pharmacokinetic parameters and BKIDC-1553 concentrations associated with efficacy in a preclinical prostate cancer mouse model. BKIDC-1553 clearance (Cl) and volume of distribution (V) in a 74 kg human were estimated by allometric scaling using pharmacokinetic parameters observed with IV dosing in rats, dogs, and non-human primates (Table S7) (36)(37)(38). Since the exponent for Cl using body weight was >1, the product of Cl x brain weight was used (39).…”

Section: Pharmacology (Pk) Absorption Distribution Metabolism and Exc...mentioning

confidence: 99%

A Compound that Inhibits Glycolysis in Prostate Cancer Controls Growth of Advanced Prostate Cancer

Ojo

Sprenger

et al. 2023

Preprint

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Metastatic castration-resistant prostate cancer remains incurable regardless of recent therapeutic advances. Tumors display highly glycolytic phenotypes as the cancer progresses. In this study, we report the preclinical activity and characterization of a novel series of small molecules with antiglycolytic activity mediated through inhibition of hexokinase 2. These compounds display selective growth inhibition across multiple prostate cancer models. We describe a lead compound (BKIDC-1553) that demonstrates promising pharmacological properties and activity in preclinical models of advanced prostate cancer. This work supports testing BKIDC-1553 and its derivatives in clinical trials for patients with advanced prostate cancer.

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Section: Pharmacology (Pk) Absorption Distribution Metabolism and Exc...mentioning

confidence: 99%

A Compound that Inhibits Glycolysis in Prostate Cancer Controls Growth of Advanced Prostate Cancer

Ojo

Sprenger

et al. 2023

Preprint

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“…In order to obtain an approximation of the peak drug level in target tissue we combine the one-compartment organ model with a one-compartment 'body' model assuming mono-exponential drug disposition characterized by the mean disposition residence time, MDRT. From equations (8) and (9) we obtain where C(0) denotes C(t = 0) and the peak level is reached at log (MDRT/ti) tmax,i = ti In the case of the two-compartment organ model we can explicitly write down the maximum of the impulse response (equation (4)) which is characterized by a peak time where a, and bi are defined by equations ( 5 ) to (7). Experimentally, this could be the peak time of the tissue concentration-time curve in an isolated organ after a bolus dose.…”

Section: Maximum Of Tissue Concentrationmentioning

confidence: 99%

On pharmacokinetics in target tissues

Weiß

1985

Biopharm & Drug Disp

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Based on a two-compartment organ model the total exposure in a target tissue, the mean tissue residence time and the peak time of the tissue concentration are evaluated in terms of tissue to blood partition coefficient and permeability coefficient (membrane permeability) of the drug, as well as the organ volume and blood flow. The total exposure is dependent upon the partition coefficient whereas the mean residence time is also affected by the permeability coefficient of the target organ. The peak time of tissue concentration following bolus intravenous injection appears to be mainly determined by the mean organ transit time and the time course of blood concentration. A tissue specific therapeutic ratio is defined using the concept of total exposure and the advantages of a local route of drug administration are discussed in this respect.

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“…Abbreviations: LVET, = left ventricular ejection time corrected for heart rate, PTQ-score = (PR X T-score)/QT, estimated from ECG, TES = total error score in Farnsworth's Munsell 100 Hue-Test calculation, pharmacokinetic model), determination of serum digoxin concentration, and further details are described in a previous paper. 3 The pharmacokinetic results represented there are replotted in Figure 1, showing that an average plateau digoxin concentration between 4 and 5ng ml-' is rapidly attained and afterwards maintained until the end of the infusion period. The total digoxin dose infused in 4 h was 1.3 mg. Six healthy male volunteers aged between 24 and 26 years participated in the study.…”

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confidence: 99%

Delay of cardiac and retinal effects of digoxin following a rapidly attained serum concentration plateau

Weiß

Sziegoleit

Fuhrmeister

et al. 1986

Biopharm & Drug Disp

Self Cite

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KEY WORDS Digoxin Effect kinetics Colour vision deficienciesMany studies have dealt with the kinetics of the pharmacologic response to digoxin following a single dose (see e.g. Kelman et al. for references). After rapid administration of a single dose, non-equilibrium conditions exist for pharmacokinetic and pharmacodynamic processes; the time course of the effect is out of phase with the time course of plasma concentration. Both the shape of the drug disposition curve and the equilibration delay between plasma and effect site determine the effect kinetics. Therefore, an appropriate pharmacokinetic model is needed to analyse the pharmacodynamics of a drug following bolus injection or oral administration.' The pharmacologic response following a rapidly attained plateau serum level, however, is exclusively determined by the equilibration process between serum concentration and effect. We therefore investigated the time course of digoxin effects (cardiac contractile performance, electrocardiographic parameters) corresponding to a serum concentration plateau of about 4.5 ng ml-' which was attained almost instantaneously from a zero value by controlled infusion. We also evaluated digoxin-induced colour vision impairment after the 4 h digoxin plateau to get some information on the kinetics of the retinal effect in comparison to the cardiac effects.The investigations were a part of an experiment which was designed to test the usefulness of controlled digoxin infusion to achieve rapidly a serum concentration plateau in normal volunteer^.^ The infusion scheme (method of

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Rapid achievement of a serum concentration plateau of digoxin through controlled infusion

Cited by 8 publications

References 10 publications

A Compound that Inhibits Glycolysis in Prostate Cancer Controls Growth of Advanced Prostate Cancer

A Compound that Inhibits Glycolysis in Prostate Cancer Controls Growth of Advanced Prostate Cancer

On pharmacokinetics in target tissues

Delay of cardiac and retinal effects of digoxin following a rapidly attained serum concentration plateau

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