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Taiwanese Journal of Obstetrics &... Mar 2022In this study, the drug kinetics of tadalafil were compared between pregnant and non-pregnant women to determine the ideal dosage to promote uterine blood flow.
OBJECTIVE
In this study, the drug kinetics of tadalafil were compared between pregnant and non-pregnant women to determine the ideal dosage to promote uterine blood flow.
MATERIALS AND METHODS
We recruited five pregnant and five non-pregnant women, all of which were administered tadalafil (20 mg/day). The blood concentration of tadalafil was measured 1, 2, 4, 6, 8, and 24 h after administration. We investigated the side effects within 4 days of tadalafil administration and compared the cumulative frequency between the two groups.
RESULTS
The mean area under the concentration-time curve and maximum blood concentration of tadalafil were not different between the pregnant and non-pregnant groups. Time to maximum blood concentration was delayed by 1 min on average in the pregnant group compared with the non-pregnant group. The cumulative frequency of side effects was significantly lower in the pregnant group than in the non-pregnant group (P = 0.026). No side effects were observed in either group after the fifth day of the tadalafil administration.
CONCLUSION
Although there was no difference in maximum blood concentration between non-pregnant and pregnant women, the rate of side effects was lower in pregnant women than in non-pregnant women. Therefore, pregnant women may tolerate tadalafil better.
Topics: Female; Fetal Growth Retardation; Humans; Placental Circulation; Pregnancy; Pregnant Women; Tadalafil
PubMed: 35361381
DOI: 10.1016/j.tjog.2022.02.009 -
Annals of Medicine and Surgery (2012) Aug 2022To date, no study evaluates the effect of atherosclerosis risk level on the efficacy of BPH drug therapies. Therefore, the present study aimed to assess the effect of...
INTRODUCTION
To date, no study evaluates the effect of atherosclerosis risk level on the efficacy of BPH drug therapies. Therefore, the present study aimed to assess the effect of atherosclerosis risk levels on the effectiveness of Tamsulosin and Tadalafil in LUTS treatment.
METHODS
The present study was a randomized clinical trial that assessed men with LUTS symptoms (at least six months). The inclusion criteria were being older than 50 years, international prostate symptom score (IPSS) ≥ 13, and maximum urinary flow rate (Qmax) between 4 and 15 ml/s. Framingham Risk Score was used to measure atherosclerosis risk. The patients were classified into four groups, including group 1: Patients with low risk and treated with Tamsulosin (0.4 mg/day), group 2: Patients with low risk and treated with Tadalafil (5 mg/day), group 3: Patients with high risk and treated with Tamsulosin (0.4 mg/day), group 4: Patients with high risk and treated with Tadalafil (5 mg/day).
RESULTS
The study included 44 and 38 patients receiving Tamsulosin and Tadalafil, respectively. The means (SD) of the baseline age for the Tamsulosin and Tadalafil groups were equal to 60.6 (6.8) and 58.8 (6.7), respectively (p-value = 0.213). The models revealed no impact of the atherosclerosis risk level on the drugs' effects (p-values = 0.378, 0.975, 0.743 for IPSS, QMAX, and VOID, respectively).
CONCLUSIONS
The present study's findings could not show the impact of atherosclerosis risk levels on the efficiency of Tamsolusin and Tadalafil in men with LUTS.
PubMed: 35846856
DOI: 10.1016/j.amsu.2022.104137 -
BMC Chemistry Jul 2022Entadfi™ is a recently FDA approved pharmaceutical combination capsule of finasteride and tadalafil. It was prescribed for the treatment of urinary tract disorders...
Entadfi™ is a recently FDA approved pharmaceutical combination capsule of finasteride and tadalafil. It was prescribed for the treatment of urinary tract disorders caused by benign prostatic hyperplasia in men. This paper introduced the first spectrophotometric methods for simultaneous determination of finasteride and tadalafil in the pure form and in the pharmaceutical capsules. UV absorption spectra of finasteride and tadalafil exhibited overlap hindered the direct simultaneous determination of the cited drugs. The UV absorption spectra of finasteride and tadalafil were transformed to the second order derivative. Finasteride could be determined selectively at 230.80 nm without interference from tadalafil. Moreover, tadalafil could be determined selectively at 292 nm without interference from finasteride. The ratio spectra of the studied drugs were derived and the derived ratio spectra of each drug were transformed to the first order derivative. Finasteride could be determined selectively at 218.80 nm without interference from tadalafil. Moreover, tadalafil could be determined selectively at 289.60 nm without interference from finasteride. The methods showed linearity with an excellent correlation coefficient in the concentration range of 10-140 µg/mL for finasteride and 3-40 µg/mL for tadalafil. The methods were validated following ICH guidelines for accuracy, precision, robustness, limit of detection, limit of quantification, and selectivity. The methods were found to be sensitive with LOD values for finasteride and tadalafil of 2.406 µg/mL and 0.876 µg/mL using the second derivative with zero crossing method and 2.229 µg/mL and 0.815 µg/mL using the first derivative of ratio spectra method. The methods were successfully applied for the determination of the studied drugs in their laboratory prepared mixtures, with mean percent recovery for finasteride and tadalafil of 99.37% and 99.17% using the second derivative with zero crossing method and 99.74% and 99.56% using the first derivative of ratio spectra method. Furthermore, the described methods were successfully applied for determination of the studied drugs in Entadfi™ capsules without interference from excipients. Based on the proposed results, the described methods could be utilized as simple method for the quality control of the studied drugs.
PubMed: 35906639
DOI: 10.1186/s13065-022-00850-w -
Shokuhin Eiseigaku Zasshi. Journal of... 2021This study determined the configuration of the isomers of tadalafil, nortadalafil, and homotadalafil in dietary supplements. The products purchased over the Internet...
This study determined the configuration of the isomers of tadalafil, nortadalafil, and homotadalafil in dietary supplements. The products purchased over the Internet studied included a honey product and a tablet, which contained tadalafil, and a candy, which contained nortadalafil and homotadalafil. Each of the pharmaceutical ingredients isolated from the products was measured with circular dichroism (CD).As a result, the CD spectrum of each isolated pharmaceutical ingredient was found to align with the standard CD spectrum of the 6R,12aR isomer, confirmed that each isolated tadalafil or tadalafil analogue included in a 6R,12aR isomer. According to a report, among the stereoisomers of tadalafil, the 6R,12aR isomers have the most potent inhibitory activities of phosphodiesterase-type-5. From the report, the potential strength of the inhibitory activity of the 6R,12aR isomers of nortadalafil and homotadalafil was suggested. Therefore, it seemed that the 6R,12aR isomer often used in the product.
Topics: Chromatography, High Pressure Liquid; Cyclic Nucleotide Phosphodiesterases, Type 5; Dietary Supplements; Magnetic Resonance Spectroscopy; Tadalafil
PubMed: 33883338
DOI: 10.3358/shokueishi.62.65 -
Pharmacology Research & Perspectives Oct 2021The COVID-19 pandemic has forced clinical studies to accommodate imposed limitations. In this study, the bioequivalence part could not be conducted as planned. Thus, the... (Randomized Controlled Trial)
Randomized Controlled Trial
The COVID-19 pandemic has forced clinical studies to accommodate imposed limitations. In this study, the bioequivalence part could not be conducted as planned. Thus, the aim was to demonstrate bioequivalence, using an adaptive study design, of tadalafil in fixed-dose combination (FDC) tablets of macitentan/tadalafil with single macitentan and tadalafil (Canadian-sourced) tablets and assess the effect of food on FDC tablets in healthy subjects. This Phase 1, single-center, open-label, single-dose, two-part, two-period, randomized, crossover study enrolled 62 subjects. Tadalafil bioequivalence as part of FDC of macitentan/tadalafil (10/40 mg) with single-component tablets of macitentan (10 mg) and tadalafil (40 mg) was determined by pharmacokinetic (PK) assessment under fasted conditions. The effect of food on FDC was evaluated under fed and fasted conditions. Fasted 90% confidence intervals (CIs) for geometric mean ratios (GMRs) were within bioequivalence limits for tadalafil and macitentan. Fed and fasted 90% CIs for area under the curve (AUC) GMR were within bioequivalence limits. However, 90% CIs for maximum plasma concentration (C ) GMR for macitentan and tadalafil were outside bioequivalence limits. One FDC-treated subject experienced a serious adverse event of transient ischemic attack (bioequivalence part). To address pandemic-imposed limitations, an adaptive study design was implemented to demonstrate that the FDC tablet was bioequivalent to the free combination of macitentan and tadalafil (Canadian-sourced). No clinically significant differences in PK were determined between fed and fasted conditions; the FDC formulation could be taken irrespective of meals. The FDC formulation under fasted and fed conditions was well tolerated with no clinically relevant differences in safety profiles between the treatment groups. NCT Number: NCT04235270.
Topics: Adult; COVID-19; Cross-Over Studies; Drug Therapy, Combination; Fasting; Female; Food-Drug Interactions; Humans; Male; Middle Aged; Pyrimidines; Research Design; Sulfonamides; Tadalafil; Therapeutic Equivalency; Young Adult
PubMed: 34624174
DOI: 10.1002/prp2.846 -
Sexual Medicine Sep 2019Erectile dysfunction (ED) is highly prevalent in aging men. Tadalafil daily and on-demand are widely used for the treatment of ED. (Review)
Review
BACKGROUND
Erectile dysfunction (ED) is highly prevalent in aging men. Tadalafil daily and on-demand are widely used for the treatment of ED.
AIM
We performed a meta-analysis to evaluate the efficacy and safety of tadalafil daily compared with tadalafil on-demand in treating men with ED after at least 24 weeks of long-term treatment.
METHODS
Randomized controlled trials of tadalafil daily vs on-demand in treating men with ED were searched using MEDLINE, EMBASE, and the Cochrane Controlled Trials Register. Systematic review was carried out using the Preferred Reporting Items for Systematic Reviews and Meta-analyses. The data was calculated by RevMan version 5.3.0. The references of related articles were also searched.
OUTCOMES
International Index of Erectile Function-Erectile Function domain, sexual encounter profile question 2 (SEP2), SEP question 3 (SEP3), any treatment-emergent adverse event (AE), discontinuation due to AEs, myalgia, back pain, headache, dyspepsia, and nasopharyngitis.
RESULTS
4 articles, including 1,035 participants were studied. The analysis found that tadalafil daily had a greater improvement than tadalafil on-demand in terms of International Index of Erectile Function-Erectile Function (mean difference (MD) 1.24; 95% CI 0.03-2.44; P = .04), SEP2 (MD 10.08; 95% CI 9.15-11.01; P < .00001) and SEP3 (MD 8.19; 95% CI 2.09-14.29; P = .009) in treating ED after at least 24 weeks treatment cycle. For safety, tadalafil on-demand had a higher incidence of any treatment-emergent AE (odds ratio 0.73; 95% CI 0.56-0.96; P = .02) compared with tadalafil daily, but for other aspects, including discontinuation due to AEs, myalgia, back pain, headache, dyspepsia, and nasopharyngitis, there were no significant difference between the 2 treatments.
CLINICAL IMPLICATIONS
Tadalafil daily may offer a better effect for ED than on-demand for long-term treatment.
STRENGTHS AND LIMITATIONS
From the perspective of evidence-based medicine, we evaluated the efficacy and safety of tadalafil daily compared with tadalafil on-demand in treating men with ED after a long-term treatment. The quality of these studies included is flawed, primarily in difference in tadalafil doses and severity of the ED.
CONCLUSION
Tadalafil daily provides a preferable therapeutic effect for ED with a lower incidence of treatment-emergent side effects relative to tadalafil on-demand after at least 24 weeks of long-term treatment. Zhou Z, Chen H, Wu J, et al. Meta-Analysis of the Long-Term Efficacy and Tolerance of Tadalafil Daily Compared With Tadalafil On-Demand in Treating Men With Erectile Dysfunction. J Sex Med 2019;7:282-291.
PubMed: 31307951
DOI: 10.1016/j.esxm.2019.06.006 -
European Review For Medical and... May 2023Premature ejaculation (PE) and erectile dysfunction (ED) are sexual dysfunction diseases affecting males. The phosphodiesterase type 5 (PDE5) inhibitors such as...
OBJECTIVE
Premature ejaculation (PE) and erectile dysfunction (ED) are sexual dysfunction diseases affecting males. The phosphodiesterase type 5 (PDE5) inhibitors such as tadalafil are used to treat ED whereas selective serotonin reuptake inhibitors (SSRIs) are preferred for PE. Most of the patients with ED also suffer from PE simultaneously. The combined drug therapies are commonly preferred as they favor elevated intra-vaginal ejaculation latency time (IELT) scores and improved sexual function. The study aimed to evaluate the efficacy and safety of daily paroxetine and tadalafil combination therapy in patients with PE and ED.
PATIENTS AND METHODS
A total of 81 PE patients with ED were enrolled in the study. Patients were treated with daily paroxetine 20 mg and tadalafil 5 mg for 4 weeks. Pre- and post-treatment IELT, premature ejaculation profile (PEP), and International Index of Erectile Function-Erectile Function (IIEF-EF) scores of the patients were analyzed.
RESULTS
The mean IELT and PEP index scores, and mean IIEF-EF values improved after combination therapy (p<0.001 for each). When lifelong and acquired PE+ED patients were compared, significant improvements were observed in IELT, PEP, and IIEF-EF scores in both groups (p<0.001).
CONCLUSIONS
Even though the treatment methods are different, combined therapies to treat simultaneous PE and ED presence are effective compared to monotherapies. However, there is still no definitive treatment that can cure all subtypes of PE or ED.
Topics: Male; Female; Humans; Erectile Dysfunction; Premature Ejaculation; Paroxetine; Tadalafil; Retrospective Studies; Ejaculation; Phosphodiesterase 5 Inhibitors; Treatment Outcome
PubMed: 37203851
DOI: 10.26355/eurrev_202305_32335 -
International Braz J Urol : Official... 2022This study aimed to assess the possible healing effect of combination treatment with a hydrogen sulfide (H2S) donor, sodium hydrosulfide (NaHS) plus tadalafil on partial...
PURPOSE
This study aimed to assess the possible healing effect of combination treatment with a hydrogen sulfide (H2S) donor, sodium hydrosulfide (NaHS) plus tadalafil on partial bladder outlet obstruction (PBOO)-induced bladder dysfunction.
MATERIALS AND METHODS
A total of 75 male Sprague-Dawley rats aged 10-wk and 300-350g were divided into five groups; control; PBOO; PBOO+NaHS (5.6mg/kg/day, i.p., 6-wk); PBOO+tadalafil (2mg/kg/day, oral, 6-wk) and PBOO+NaHS+tadalafil. PBOO was created by partial urethral ligation. 6 weeks after obstruction, the in vitro contractile responses of the detrusor muscle and Western blotting, H2S and malondialdehyde assay were performed in bladder tissues.
RESULTS
There was an increase in bladder weight(p<0.001) and a decrease in contractile responses to KCL(p<0.001), carbachol(p<0.01), electrical field stimulation(p<0.05) and ATP (p<0.001) in the detrusor smooth muscle of obstructed rats which was normalized after the combination treatment. Cystathionine γ-lyase and cystathionine β-synthase, and nuclear factor kappa B protein levels did not significantly differ among groups. The obstruction induced decrement in 3-mercaptopyruvate sulfur transferase protein expression(p<0.001) and H2S levels(p<0.01) as well as increment in protein expressions of neuronal nitric oxide synthase (NO, p<0.001), endothelial NOS (p<0.05), inducible NOS(p<0.001), hypoxia-inducible factor 1-alpha (p<0.01), and malondialdehyde levels (p<0.01), when combined treatment entirely normalized.
CONCLUSIONS
Combination therapy has beneficial effects on bladder dysfunction via regulating both H2S and nitric oxide pathways as well as downregulation of oxidative stress and hypoxia. The synergistic effect of H2S and nitric oxide is likely to modulate bladder function, which supports the combined therapy for enhancing clinical outcomes in men with BPH/LUTS.
Topics: Adenosine Triphosphate; Animals; Carbachol; Cystathionine beta-Synthase; Cystathionine gamma-Lyase; Hydrogen Sulfide; Hypoxia; Hypoxia-Inducible Factor 1; Male; Malondialdehyde; NF-kappa B; Nitric Oxide; Nitric Oxide Synthase Type I; Oxidative Stress; Rats; Rats, Sprague-Dawley; Sulfides; Sulfur; Tadalafil; Transferases; Urinary Bladder; Urinary Bladder Neck Obstruction
PubMed: 36173409
DOI: 10.1590/S1677-5538.IBJU.2022.0207 -
British Journal of Clinical Pharmacology Dec 2020To demonstrate the bioequivalence of macitentan/tadalafil fixed-dose combination (FDC) tablets with single-component tablets of macitentan and tadalafil in healthy...
AIMS
To demonstrate the bioequivalence of macitentan/tadalafil fixed-dose combination (FDC) tablets with single-component tablets of macitentan and tadalafil in healthy subjects.
METHODS
Studies AC-077-101 and AC-077-103 were single-centre, open-label, single-dose, 2-period, randomized, crossover Phase 1 studies conducted in healthy subjects. Two FDCs were investigated: FDC-1 and FDC-2 in Study AC-077-101 and FDC-2 in Study AC-077-103. Both FDCs contained 10 mg/40 mg of macitentan/tadalafil and differed in excipients and coating materials used. In both studies, pharmacokinetic sampling over 216 hours was conducted, and pharmacokinetic parameters were derived using noncompartmental methods.
RESULTS
Bioequivalence of macitentan, its active metabolite ACT-132577, and tadalafil was established for FDC-2 in both studies AC-077-101 and AC-077-103 in which tadalafil as a single component was sourced from the USA and EU, respectively, to fulfil regional regulatory requirements. The area under the plasma concentration-time curve and maximum plasma concentration with 90% confidence intervals of all components were entirely within the bioequivalence limits (0.8000-1.2500). No subject died and no serious adverse events were reported in either studies.
CONCLUSION
The FDC-2 tablet containing 10 mg/40 mg of macitentan/tadalafil was bioequivalent to the free combination of 10 mg macitentan and 40 mg tadalafil (both US and EU sourced). Macitentan and tadalafil were well tolerated when administered as FDC or as a free combination.
Topics: Adolescent; Adult; Area Under Curve; Cross-Over Studies; Delayed-Action Preparations; Drug Combinations; Female; Healthy Volunteers; Humans; Hypoglycemic Agents; Male; Metformin; Middle Aged; Pyrimidines; Sulfonamides; Tablets; Tadalafil; Therapeutic Equivalency; Young Adult
PubMed: 32374030
DOI: 10.1111/bcp.14347 -
British Journal of Pharmacology Dec 2020PDE type 5 inhibitors (PDE5Is), such as sildenafil, tadalafil and vardenafil, are a class of drugs used to prolong the physiological effects of NO/cGMP signalling in... (Review)
Review
PDE type 5 inhibitors (PDE5Is), such as sildenafil, tadalafil and vardenafil, are a class of drugs used to prolong the physiological effects of NO/cGMP signalling in tissues through the inhibition of cGMP degradation. Although these agents were originally developed for the treatment of hypertension and angina, unanticipated side effects led to advances in the treatment of erectile dysfunction and, later, pulmonary arterial hypertension. In the last decade, accumulating evidence suggests that PDE5Is may confer a wider range of clinical benefits than was previously recognised. This has led to a broader interest in the cardiovascular therapeutic potential of PDE5Is, in conditions such as hypertension, myocardial infarction, stroke, peripheral arterial disease, chronic kidney disease and diabetes mellitus. Here, we review the pharmacological properties and established licensed uses of this class of drug, along with emerging therapeutic developments and possible future indications.
Topics: Cardiovascular Diseases; Erectile Dysfunction; Humans; Hypertension; Male; Phosphodiesterase 5 Inhibitors; Sildenafil Citrate; Tadalafil
PubMed: 31721165
DOI: 10.1111/bph.14920