Pharmacokinetics and bioavailability of pentoxifylline in healthy volunteers-a comparative study of three oral formulations

Pokrajac, M.; Miljković, Branislava; Simić, Dragan; Brzaković, Branka; Galetin, Aleksandra

doi:10.1016/s0939-6411(96)00015-x

Cited by 13 publications

(13 citation statements)

References 6 publications

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“…Extensive metabolic transformations and processes reversibility are responsible for the low and variable bioavailability of the drug (Pokrajac et al, 1997;Magnusson et al, 2006). The analytical techniques used to assay PTX and related metabolites may also add enhanced variability to the fi nal quantitative results, as extensive sample manipulation steps induce experimental errors in addition to the intrinsic response variability of the detection equipments (especially when using MS or MS/MS ones).…”

Section: Introductionmentioning

confidence: 99%

Bioanalysis of pentoxifylline and related metabolites in plasma samples through LC‐MS/MS

Sora¹,

Cristea²,

Albu³

et al. 2009

Biomedical Chromatography

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Analytical aspects related to the assay of pentoxifylline (PTX), lisofylline (M1) and carboxypropyl dimethylxanthine (M5) metabolites are discussed through comparison of two alternative analytical methods based on liquid chromatography separation and atmospheric pressure electrospray ionization tandem mass spectrometry detection. One method is based on a 'pure' reversed-phase liquid chromatography mechanism, while the second one uses the additional polar interactions with embedded amide spacers linking octadecyl moieties to the silicagel surface (C-18 Aqua stationary phase). In both cases, elution is isocratic. Both methods are equally selective and allows separation of unknowns (four species associated to PTX, two species associated to M1) detected through specific mass transitions of the parent compounds and owning respective structural confirmation. Plasma concentration-time patterns of these compounds follow typical metabolic profiles. It has been advanced that in-vivo formation of conjugates of PTX and M1 is possible, such compounds being cleaved back to the parent ones within the ion source. The first method was associated with a sample preparation procedure based on plasma protein precipitation by strong organic acid addition. The second method used protein precipitation by addition of a water miscible organic solvent. Both analytical methods were fully validated and used to assess bioequivalence between a prolonged release generic formulation and the reference product, under multidose and single dose approaches.

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Section: Introductionmentioning

confidence: 99%

Bioanalysis of pentoxifylline and related metabolites in plasma samples through LC‐MS/MS

Sora¹,

Cristea²,

Albu³

et al. 2009

Biomedical Chromatography

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“…4,5 As per the literature, there were many HPLC methods reported for the estimation of PTF using UV detection in biological matrix. [6][7][8][9][10][11][12][13][14][15][16][17][18][19] However, sensitivity, resolution, and time must be sacrificed by these conventional methods. There were few LC-MS methods proposed for quantification of PTF alone or along with its metabolites.…”

Section: Pentoxifyllinementioning

confidence: 99%

Development and validation of bioanalytical liquid chromatography–tandem mass spectrometry method for the estimation of pentoxifylline in human plasma: Application for a comparative pharmacokinetic study

Dodda

Ajitha

Polagani³

et al. 2018

Eur J Mass Spectrom (Chichester)

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A method for bioanalysis of pentoxifylline in human plasma was developed using liquid chromatography–tandem mass spectrometry, which is simple, specific, and sensitive. Pentoxifylline D5 was used as the internal standard. Employing only 100 µl of human plasma, processing was done with solid-phase extraction technique. The analyte and the internal standard were separated from endogenous components on Ace phenyl column using a mixture of 5 mM ammonium acetate buffer and high performance liquid chromatography grade acetonitrile (60:40, v/v) as mobile phase at a flow rate of 1 ml/min. The linearity of the method was in the range of 3–1200 ng/ml with r2 > 0.99. Positive ion MRM mode was used for the detection of the analyte and the internal standard. The method was validated as per the US Food and Drug Administration guidelines and the results were within the acceptance limits. The proposed method was applied for comparative pharmacokinetic study of pentoxifylline after oral administration of 400 and 600 mg tablets to South Indian male subjects under fed conditions.

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“…Pentoxifylline was used as a model drug since it has a short half-life of 1-2 hours, 23 high density, 24 and is highly soluble in water (191 mg/mL at 37°C). 25 The variables that may affect drug release and floating properties were investigated, such as wet granulation (to compare effects of powders versus those of granules), type and the ratio of gas-forming agent.…”

Section: Introductionmentioning

confidence: 99%

Influence of calcium carbonate and sodium carbonate gassing agents on pentoxifylline floating tablets properties

2017

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Purpose: this study was to design and evaluate effervescent floating tablets with sustained release behaviour. Pentoxifylline is a water-soluble model drug with a short half-life, consequently developing sustained release preparations would be beneficial. Methods: a binary (1:1) mixture of sodium alginate and hydroxyethyl cellulose containing pentoxifylline, with either 10% or 20% calcium carbonate or sodium carbonate, was used to prepare floating tablets. Results: tablets floated on the surface of the dissolution medium, showed an adequate floating lag time, and floated for more than 12 hours. Tablets manufactured from granules with 20%(w/w) calcium carbonate were promising with respect to their floating lag time (~7min), floating duration (>24 hours), sustained drug release rate, and swelling ability. An in vivo study of these promising tablets and a reference solution of pentoxifylline were investigated following oral administration of 5.75±0.15mg in rats. Compared with the reference solution, the pharmacokinetic parameters changed significantly (p<0.05); the Cmax of the tablets was decreased (945.32ng/ml versus 2552.30ng/ml for the solution), while the Tmax and t1/2 were prolonged. Conclusion: the study shows that a binary mixture of hydroxyethyl cellulose and sodium alginate, together with 20%(w/w) calcium carbonate, offers an exciting opportunity to develop sustained release pentoxifylline preparations.

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Pharmacokinetics and bioavailability of pentoxifylline in healthy volunteers-a comparative study of three oral formulations

Cited by 13 publications

References 6 publications

Bioanalysis of pentoxifylline and related metabolites in plasma samples through LC‐MS/MS

Bioanalysis of pentoxifylline and related metabolites in plasma samples through LC‐MS/MS

Development and validation of bioanalytical liquid chromatography–tandem mass spectrometry method for the estimation of pentoxifylline in human plasma: Application for a comparative pharmacokinetic study

Influence of calcium carbonate and sodium carbonate gassing agents on pentoxifylline floating tablets properties

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