Application of Statistical Moment Theory to Pharmacokinetics

Mayer, Philip; Brazzell, Romulus K.

doi:10.1002/j.1552-4604.1988.tb03164.x

Cited by 15 publications

(10 citation statements)

References 14 publications

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“…Unlike half-life, MRT is a composite of drug distribution and elimination, thus representing a useful index of the average time a drug remains in the body. MRT is derived by dividing the area under the first moment curve (AUMC) by AUC, using statistical moment theory (Mayer & Brazzell, 1988). Furthermore, maximal testosterone concentration (Cmax) and time to Cm,,( T,,,) were calculated.…”

Section: Discussionmentioning

confidence: 99%

Pharmacokinetics and pharmacodynamics of subcutaneous testosterone implants in hypogonadal men

Jockenhövel¹,

Vogel²,

Kreutzer³

et al. 1996

Clinical Endocrinology

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Section: Discussionmentioning

confidence: 99%

Pharmacokinetics and pharmacodynamics of subcutaneous testosterone implants in hypogonadal men

Jockenhövel¹,

Vogel²,

Kreutzer³

et al. 1996

Clinical Endocrinology

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“…Time taken to achieve maximal plasma concentration following per os administration (T ) was max calculated using differential calculus. Data were further analyzed using noncompartmental methods according to the statistical moment theory (Mayer & Brazzell, 1988). The results are presented as means and standard deviations, except for pharmacokinetic parameters not normally distributed, which are presented as medians and median deviations.…”

Section: Bioassaymentioning

confidence: 99%

Comparison of oral erythromycin formulations in the horse using pharmacokinetic profiles

Ewing

Burrows

MacAllister

et al. 1994

Vet Pharm & Therapeutics

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Ewing, P. J., Burrows, G., MacAllister, C, Clarke, C. Comparison of oral erythromycin formulations in the horse using pharmacokinetic profiles. J. vet. Pharmacol, Therap.17, 17–23. The pharmacokinetic properties of four erythromycin formulations were compared in six adult horses after administration of single and multiple oral doses. Formulations of erythromycin administered were estolate and phosphate given 37.5 mg/kg every 12 h and 25 mg/kg every 8 h, and stearate and ethylsuccinate given 25 mg/kg every 8 h. Areas under the curve (AUC) and maximum plasma erythromycin concentrations (Cmax) were equal or greater (P ≥ 0.05) following administration of erythromycin phosphate and stearate compared with those values following administration of erythromycin estolate or ethylsuccinate. In comparing an 8 h vs. a 12 h dosage interval for multiple doses of erythromycin phosphate or estolate, there were no significant differences observed in AUC(24–28 h), peak‐trough plasma concentrations or duration that plasma concentrations exceeded the minimal inhibitory concentration (MIC) for Rhodococcus equi. Comparisons of pharmacokinetic parameters between single and multiple doses were made for each formulation. Differences in Cmax, tmax, or t½β between single and multiple doses were demonstrated for erythromycin ethylsuccinate and estolate. Based on equivalent plasma antibiotic concentrations, erythromycin phosphate or stearate could be substituted for estolate in the treatment of Rhodococcus equi pneumonia. Furthermore, there was no advantage of an 8‐h interval, compared with an interval of 12 h.

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“…The elimination half-life, t 1/2,z , was obtained by log-linear regression of the terminal phase of the plasma concentration-time profile after the last dose on days 7-9. Mean residence time (MRT) was calculated by a standard formula [15]. Dose proportionality was assessed by linear regression of a logarithmic transformation of the power function y = a.x b , where y = AUC ss or C max,ss , x = dose and a , b are coefficients [16].…”

Section: Discussionmentioning

confidence: 99%

Pharmacokinetics and pharmacodynamics of terbogrel, a combined thromboxane A₂ receptor and synthase inhibitor, in healthy subjects

Guth¹,

Narjes

Schubert³

et al. 2004

Brit J Clinical Pharma

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AimsTo characterize the pharmacokinetics of terbogrel, a new combined thromboxane A 2 (TxA 2 ) receptor and synthase inhibitor, in healthy human subjects after single or multiple oral administration. MethodsForty-eight healthy male subjects received a single oral dose (10, 25, 50, 100, 150 or 200 mg) of terbogrel or placebo and 32 different subjects received one of the following treatments twice daily for 7 days: 50, 100 or 150 mg terbogrel, placebo, or once-a-day 330 mg acetylsalicylic acid. ResultsTerbogrel was well tolerated without obvious adverse effects following either a single oral dose or administration over 7 days. Plasma drug concentrations were dose-linear and there was no accumulation over 7 days. There was a dose-dependent blockade of TxA 2 receptors and of inhibition of thromboxane synthase activity with values for I C 50 of 12 ng ml -1 and 6.7 ng ml -1 , respectively. At the highest dose tested (150 mg) there was almost complete inhibition of thomboxane synthase and thromboxane receptor occupancy. Even at trough concentrations, receptor occupancy remained above 80% and thromboxane synthase was still completely inhibited. These two activities were associated with a dose-dependent inhibition of platelet agg regation ( > 80% at the 150 mg dose of terbogrel) and enhanced prostacyclin production. ConclusionsTerbogrel is a potent agent having two distinct, complimentary pharmacodynamic actions, namely inhibition of thromboxane synthase and antagonism of the TxA 2 receptor. The antithrombotic effect of terbogrel was dose-dependent and was associated with enhanced prostacyclin production. Terbogrel is an attractive candidate for long-term antithrombotic therapy.

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Application of Statistical Moment Theory to Pharmacokinetics

Cited by 15 publications

References 14 publications

Pharmacokinetics and pharmacodynamics of subcutaneous testosterone implants in hypogonadal men

Pharmacokinetics and pharmacodynamics of subcutaneous testosterone implants in hypogonadal men

Comparison of oral erythromycin formulations in the horse using pharmacokinetic profiles

Pharmacokinetics and pharmacodynamics of terbogrel, a combined thromboxane A₂ receptor and synthase inhibitor, in healthy subjects

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Application of Statistical Moment Theory to Pharmacokinetics

Cited by 15 publications

References 14 publications

Pharmacokinetics and pharmacodynamics of subcutaneous testosterone implants in hypogonadal men

Pharmacokinetics and pharmacodynamics of subcutaneous testosterone implants in hypogonadal men

Comparison of oral erythromycin formulations in the horse using pharmacokinetic profiles

Pharmacokinetics and pharmacodynamics of terbogrel, a combined thromboxane A2 receptor and synthase inhibitor, in healthy subjects

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Product

Resources

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Pharmacokinetics and pharmacodynamics of terbogrel, a combined thromboxane A₂ receptor and synthase inhibitor, in healthy subjects