Population Dose-Response Model for Tadalafil in the Treatment of Male Erectile Dysfunction

Staab, Alexander; Tillmann, Christiane; Forgue, S. Thomas; Mackie, Alison E.; Allerheiligen, Sandra R. B.; Rapado, Javier; Trocóniz, Iñaki F.

doi:10.1023/b:pham.0000036922.03519.40

Cited by 14 publications

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“…Age, weight, diabetic status and renal status (creatinine clearance) had no statistically significant effects on tadalafil clearance or distribution volume [26]. Furthermore, no effect of age was found in pharmacodynamic modelling of ED outcome measures as a function of tadalafil dose or systemic exposure [27]. Diabetic status was confounded with ED severity at baseline, possibly masking an independent effect of this condition in that report.…”

Section: Discussionmentioning

confidence: 67%

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Effects of gender, age, diabetes mellitus and renal and hepatic impairment on tadalafil pharmacokinetics

Forgue

Phillips

Bedding³

et al. 2006

Brit J Clinical Pharma

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AimsTo evaluate the effects of gender, age, diabetes mellitus, renal and hepatic impairment on tadalafil pharmacokinetics and tolerability. MethodsSix single-dose (5, 10 or 20 mg orally) clinical pharmacology studies were conducted in the UK, Belgium, Poland and Germany in healthy male and female subjects, elderly subjects and subjects with diabetes mellitus, renal impairment, end-stage renal failure (ESRF) or hepatic impairment. The gender study also incorporated administration of 10 mg tadalafil daily for 10 days. ResultsSystemic exposure in the elderly was 25% greater than in young subjects (mean AUC ratio 1.25; 90% confidence interval 0.972, 1.61). The AUC was 19% lower in subjects with diabetes mellitus than in healthy age/gender-matched controls. Pharmacokinetics in female subjects were essentially similar to those in males. Exposure in subjects with mild or moderate renal insufficiency was approximately twice that in healthy subjects. The mean AUC for the major metabolite (total methylcatechol glucuronide) in the presence of ESRF was three times the mean for healthy subjects. Haemodialysis contributed negligibly to elimination of tadalafil or the metabolite. Hepatic impairment had negligible effects on exposure. The most common adverse events in these six studies were headache, back pain and myalgia. A 10-mg dose was not well tolerated by subjects with moderate renal dysfunction in this study. ConclusionsNo clinically significant effect of gender, age, diabetes mellitus or hepatic impairment on tadalafil pharmacokinetics was observed. Renal insufficiency resulted in increased systemic exposure. Tadalafil was not associated with any serious clinically significant adverse events or study discontinuations due to adverse events.

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Section: Discussionmentioning

confidence: 67%

“…142 (26) 140 (21) 196 (27) 183 (25) 193 (22) 184 (27) 183 (31) 217 (21) 220 (22) 180 (38) 133 (21) 146 (23) 101 ( …”

Section: Safety Assessmentunclassified

Effects of gender, age, diabetes mellitus and renal and hepatic impairment on tadalafil pharmacokinetics

Forgue

Phillips

Bedding³

et al. 2006

Brit J Clinical Pharma

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“…37 ED severity was identified to account for a large portion of the between-patient variability in the dose-response relationship, with greater improvement in erectile function in more severely affected individuals. 27,37 The absolute performance at any dose level, however, was the highest in the least severely affected individuals. The tadalafil doses required to achieve half-maximal improvement (ED 50 ) as quantified by the International Index of Erectile Function questionnaire were 4.7, 7.1, and 10.1 mg for patients with mild, moderate, and severe ED, respectively.…”

Section: Elimination Of Pde5 Inhibitorsmentioning

confidence: 99%

“…The tadalafil doses required to achieve half-maximal improvement (ED 50 ) as quantified by the International Index of Erectile Function questionnaire were 4.7, 7.1, and 10.1 mg for patients with mild, moderate, and severe ED, respectively. 15,37 PDE selectivity and adverse events The pharmacodynamics of PDE5 inhibitors are determined by their potency and selectivity towards PDE inhibition. Sildenafil, vardenafil, and tadalafil all differ in their potency and selectivity for the 11 known PDE families, which gives rise to differences in their activity and side effect profiles.…”

Section: Elimination Of Pde5 Inhibitorsmentioning

confidence: 99%

The role of pharmacokinetics and pharmacodynamics in phosphodiesterase-5 inhibitor therapy

et al. 2006

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Differences in clinical pharmacology of the currently marketed phosphodiesterase (PDE)5 inhibitors sildenafil, vardenafil and tadalafil are largely determined by their pharmacokinetic (PK) properties and their PDE5 inhibitory activity profile. This review outlines the basic concepts of pharmacokinetics and pharmacokinetic pharmacodynamic (PK/PD) relationships and their relevance to dose selection and applied pharmacotherapy. It is followed by a detailed comparative discussion on the pharmacokinetics and exposure-response relationship of the currently available PDE5 inhibitors, including known drug-drug interactions and dosage adjustments in special populations. The review is aimed at providing a critical assessment of the pharmacokinetics of PDE5 inhibitors, which may assist clinicians in tailoring drug and/or treatment regimens to the unique needs of each individual patient with erectile dysfunction.

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“…The time course of oral absorption could successfully be modeled by a rapid first-order process. Population estimates of the first-order absorption rate constant from phase II and phase III studies are 1.75 and 1.86 hours -1 , respectively [123]. The absorption and pharmacodynamic properties of tadalafil are not affected by either food or alcohol, and thus the drug can be administered without regard for food or alcohol consumption [124].…”

Section: Tadalafilmentioning

confidence: 99%

Pharmacological Potential of PDE5 Inhibitors for the Treatment of Cystic Fibrosis

Lubamba¹,

Dhooghe²,

Noël³

et al. 2012

Cystic Fibrosis - Renewed Hopes Through Research

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Population Dose-Response Model for Tadalafil in the Treatment of Male Erectile Dysfunction

Cited by 14 publications

References 26 publications

Effects of gender, age, diabetes mellitus and renal and hepatic impairment on tadalafil pharmacokinetics

Effects of gender, age, diabetes mellitus and renal and hepatic impairment on tadalafil pharmacokinetics

The role of pharmacokinetics and pharmacodynamics in phosphodiesterase-5 inhibitor therapy

Pharmacological Potential of PDE5 Inhibitors for the Treatment of Cystic Fibrosis

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