Determination of dapoxetine, an investigational agent with the potential for treating depression, and its mono- and di-desmethyl metabolites in human plasma using column-switching high-performance liquid chromatography

Hamilton, Cristi L.; Cornpropst, J.David

doi:10.1016/0378-4347(93)80171-y

Cited by 22 publications

(16 citation statements)

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“…Dapoxetine was originally developed as a drug for the treatment of depression [4,5]. The chemical formula of dapoxetine (LY210448) was originally produced by Eli Lilly, and aimed to be an antidepressant (SSRI) [4,5]. The compound is structurally related to fluoxetine from the same manufacturer.…”

Section: Resultsmentioning

confidence: 99%

“…The compound is structurally related to fluoxetine from the same manufacturer. Because fluoxetine is an SSRI with a long half‐life (the longest half‐life of all licensed SSRIs), Eli Lilly became interested in “developing” an SSRI with a short half‐life for the treatment of depression [4,5]. Their program with dapoxetine initially started with phase I clinical trials in the United States [4,5].…”

Section: Resultsmentioning

confidence: 99%

“…Because fluoxetine is an SSRI with a long half‐life (the longest half‐life of all licensed SSRIs), Eli Lilly became interested in “developing” an SSRI with a short half‐life for the treatment of depression [4,5]. Their program with dapoxetine initially started with phase I clinical trials in the United States [4,5]. However, in 2000, PPD GenuPro, which was established from a collaboration between Eli Lilly and Pharmaceutical Product Development (PPD), granted a license for dapoxetine to ALZA Corporation, a completely owned subsidiary of Johnson & Johnson.…”

Section: Resultsmentioning

confidence: 99%

“…decided to withdraw their compound UK‐390,957 from further clinical studies. However, ALZA Inc., currently part of Johnson & Johnson Inc., pioneered “dapoxetine” in men with complaints of PE [4,5]. The situation today is that the Food and Drug Administration (FDA) has decided critically to turn down all registration files on dapoxetine, while a final decision of the European registration authorities (EMEA) is still pending.…”

Section: Introductionmentioning

confidence: 99%

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Premature Ejaculation and Pharmaceutical Company-Based Medicine: The Dapoxetine Case

Waldinger

Schweitzer

2008

The Journal of Sexual Medicine

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Introduction The manufacturer of dapoxetine funded randomized clinical trials to study its effect in premature ejaculation (PE). Financial support by pharmaceutical companies, however, may jeopardize the neutrality of clinical research. Aim To investigate the scientific process that has been followed in dapoxetine treatment trials and reviews as compared to daily drug treatment trials and reviews with selective serotonin reuptake inhibitors (SSRIs) in men with PE. Methods A search of Medline and Embase was conducted using the search terms “dapoxetine” or “SSRI.” References of retrieved articles were searched. Only studies describing the use of these drugs in men with PE were included. Main Outcome Measures Compared fold-increase intravaginal ejaculation latency time (IELT), geometric mean IELT, and adverse effect profiles between dapoxetine and SSRIs in PE. Results Preclinical studies on dapoxetine, including a multicenter study (category A) and reviews (category B), were compared with clinical studies with daily conventional SSRIs in PE (category C). Categories A/B focused on patient-reported outcomes with less attention for the IELT. The ejaculation-delaying effect of dapoxetine was expressed as natural mean IELT rather than as geometrical mean IELT. Dapoxetine side effects were monthly scored. In contrast, a significant part of category C articles focused on IELT data, used geometric mean IELT outcomes, and one study reported the side effects measured 24–48 hours after drug intake using a validated questionnaire. Without the Food and Drug Administration approval, dapoxetine, as well as other SSRIs in PE, is an off-label drug for PE. However, the off-label use of dapoxetine has never been criticized by clinical investigators in contrast to commentaries against the off-label use of daily SSRI treatment in PE. Conclusions Manufacturer-funded drug treatment research (categories A and B) is advantageously treated by some authors as compared with nonfunded trials with daily conventional SSRIs (category C). PE drug treatment research is a young and dynamic field, and its development deserves transparency to its development.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Premature Ejaculation and Pharmaceutical Company-Based Medicine: The Dapoxetine Case

Waldinger

Schweitzer

2008

The Journal of Sexual Medicine

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“…HPLC methods have also been reported for determination of DP enantiomer, process related impurities and metabolites in pharmaceutical preparations and/or biological samples [21][22][23].…”

Section: Introductionmentioning

confidence: 99%

Validated Stability-Indicating Derivative Spectrophotometry and Synchronous Fluorescence Spectroscopy Methods for the Determination of Dapoxetine Hydrochloride in the Presence of its Degradation Product and Co-Formulated Drugs

Soliman¹,

El-Agizy²,

Bayoumi³

2017

Pharm Anal Acta

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The stability of dapoxetine hydrochloride (DP) was studied in the presence of its acidic degradation product namely, (+)-N, N-dimethyl-1-phenyl-3-propanolamine (Deg 1) and the co-formulated drugs Vardenafil (VR) and Tadalafil (TD) using derivative spectrophotometry and synchronous fluorescence spectroscopy methods.Method I, stability indicating derivative spectrophotometry 1D was developed for the determination of DP in the presence of its hydrolytic degradation product and the co-formulated drug VR. The amplitude of the first derivative spectra 1D at λmax of 240 nm and 227 nm was measured for DP and VR, respectively.Method IIA, stability indicating synchronous fluorescence spectroscopy (SFS) was described for the determination of DP in the presence of its hydrolytic degradation product and the co-formulated drug TD. In this method (SFS) was performed at ∆λ of 70 nm in acetonitrile medium and the synchronous fluorescence intensities of TD were measured at 212 nm.Method IIB, The first derivative synchronous fluorescence spectra FDSFS were applied for measuring the amplitudes of FDSFS at 295 nm and 242 nm for analysis of DP and TD, respectively.The degradation products was obtained in acidic stress condition of 5 M hydrochloric acid, separated, and identified by IR and mass spectrometry to confirm its structure, and elucidate degradation pathway. The methods were applied for stability-indicating assay of DP (method I and II), VR (method I) and TD (method II) in bulk powders, laboratory prepared mixtures and co-formulated pharmaceutical preparations containing degradation product of DP. The results obtained were satisfactory compared with those obtained from the comparison methods and no significant differences were found. The two stability indicating methods were validated as per ICH guidelines.

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Disposition of ¹⁴C‐dapoxetine in rats: Complementary experiments with whole‐body autoradiographic and tissue dissection techniques

Bernstein

Manzione

Pohland

et al. 1994

Biopharm & Drug Disp

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Tissue distribution studies, utilizing whole-body autoradiography and organ dissection techniques, were conducted in male Fischer 344 rats following the oral administration of 14C-dapoxetine HCl, a potent serotonin reuptake inhibitor. The preliminary study using whole-body autoradiography proved invaluable in locating radioactivity in an organ not usually harvested in a tissue distribution study, namely the preputial gland. Selected organs, based on whole-body autoradiography findings, were dissected from rats and analyzed for radiocarbon content by liquid scintillation counting and for parent drug and N-dealkylated metabolites by extraction and HPLC analysis. Highest concentrations of radiocarbon were observed in the organs of absorption and elimination (ileum, cecum, stomach, duodenum, liver, colon, and kidney) but notable quantities were observed in the lung and preputial and Harderian glands. Most tissues had returned to background radioactive levels 72 h after dosing but persistent concentrations of radiocarbon were present in the preputial gland and liver one week after the single dose of 14C-dapoxetine. Analysis by HPLC demonstrated the presence of parent drug and N-desmethyl metabolite (nor-dapoxetine) in those organs examined; however, the majority of the radioactivity remained unidentified.

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Determination of dapoxetine, an investigational agent with the potential for treating depression, and its mono- and di-desmethyl metabolites in human plasma using column-switching high-performance liquid chromatography

Cited by 22 publications

References 2 publications

Premature Ejaculation and Pharmaceutical Company-Based Medicine: The Dapoxetine Case

Premature Ejaculation and Pharmaceutical Company-Based Medicine: The Dapoxetine Case

Validated Stability-Indicating Derivative Spectrophotometry and Synchronous Fluorescence Spectroscopy Methods for the Determination of Dapoxetine Hydrochloride in the Presence of its Degradation Product and Co-Formulated Drugs

Disposition of ¹⁴C‐dapoxetine in rats: Complementary experiments with whole‐body autoradiographic and tissue dissection techniques

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Determination of dapoxetine, an investigational agent with the potential for treating depression, and its mono- and di-desmethyl metabolites in human plasma using column-switching high-performance liquid chromatography

Cited by 22 publications

References 2 publications

Premature Ejaculation and Pharmaceutical Company-Based Medicine: The Dapoxetine Case

Premature Ejaculation and Pharmaceutical Company-Based Medicine: The Dapoxetine Case

Validated Stability-Indicating Derivative Spectrophotometry and Synchronous Fluorescence Spectroscopy Methods for the Determination of Dapoxetine Hydrochloride in the Presence of its Degradation Product and Co-Formulated Drugs

Disposition of 14C‐dapoxetine in rats: Complementary experiments with whole‐body autoradiographic and tissue dissection techniques

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Disposition of ¹⁴C‐dapoxetine in rats: Complementary experiments with whole‐body autoradiographic and tissue dissection techniques