Bioavailability of 11 phenytoin products

Melikian, Armen P.; Straughn, Arthur B.; Slywka, Gerald W.A.; Whyatt, Philip L.; Meyer, Marvin C.

doi:10.1007/bf01066217

Cited by 34 publications

(18 citation statements)

References 6 publications

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“…These results were in agreement with previously published studies using plasma (Schumaker and Metzler 1998;Melikian et al 1977), suggesting that saliva is fairly comparable to plasma fluid in relative bioavailability studies of PHT. Therefore, we believe that saliva is not only suitable as the monitored biological fluid in RBA studies, but also a more convenient tool since it provides analog information but with major analytical and ethical advantages.…”

Section: Discussionsupporting

confidence: 94%

“…The study by Melikian et al (1977), which presents pharmacokinetic parameters of phenytoin in plasma calculated after performing an RBA study of 11 commercial products of PHT 100 mg IR capsules in healthy volunteers, was used. Computing the ratios between (S/P T ratios) salivary AUC 0-t (for R and T formulations) and plasma AUC 0-t [of the 11 formulations assayed (Melikian et al 1977)], a mean ± SD of 0.112 ± 0.009 was obtained (range: 0.097-0.128), which represents a quite good estimation of the mean S/P T ratio = 0.10 expected for PHT (Goodman and Gilman 2006;Moffat et al 2004). However, if that calculation is repeated for C max , a higher value is obtained: 0.173 ± 0.027 (range: 0.142-0.226).…”

Section: Discussionmentioning

confidence: 99%

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Is saliva suitable as a biological fluid in relative bioavailability studies? Analysis of its performance in a 4 × 2 replicate crossover design

Ruiz

Fagiolino

Buschiazzo

et al. 2011

Eur J Drug Metab Pharmacokinet

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The aim of the present study was to evaluate the suitability of saliva as a biological fluid in relative bioavailability (RBA) studies, with the focus on the statistical design and data variability. A randomized, open-label, four periods and two sequences (4 × 2) crossover RBA study in saliva of two phenytoin (PHT) 100 mg immediate-release capsules was performed. PHT is a narrow therapeutic index drug that has been widely used for epilepsy treatment for many years. Published information regarding its bioavailability is available, but plasma assessed. This study was designed and performed using saliva as the biological fluid and the simplest conditions that produce coherent results with previously published plasma studies. Pharmacokinetic parameters (C (max), T (max), AUC(0-t ), AUC(0-inf), C (max)/AUC(0-t ), K (e), and t (1/2)) for each volunteer at each period were calculated. Four different BE calculations were performed: individual bioequivalence, by the method of moments, and three average bioequivalence with data averaged over the two administrations and with data of periods 1-2 and 3-4. ANOVA calculation showed no significant subject-by-formulation interaction, period and sequence effects. The intra-subject variabilities were at least 20-fold lower than the inter-subject ones for C (max), AUC(0-t ) and AUC(0-inf). In all four BE calculations, the 90% CIs for the T/R ratios of studied pharmacokinetics parameters fell within the 80-125% range proposed by most regulatory agencies.

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Section: Discussionsupporting

confidence: 94%

Section: Discussionmentioning

confidence: 99%

Is saliva suitable as a biological fluid in relative bioavailability studies? Analysis of its performance in a 4 × 2 replicate crossover design

Ruiz

Fagiolino

Buschiazzo

et al. 2011

Eur J Drug Metab Pharmacokinet

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“…Inter-individual differences have been documented for imipramine (1), propranolol (2) and rifampicin (3) while inter-brand differences have been reported for phenytoin (4) and digoxin (5). Therefore, prudence speaks for conducting comparative bioavailability studies for any new formulation before it is made available for clinical use.…”

Section: Introductionmentioning

confidence: 99%

Comparative bioavailability and in-vitro antimicrobial activity of two different brands of rifampicin

Garg

Chakrabarti

Panigrahi

et al. 1991

European Journal of Drug Metabolism and Pharmacokinetics

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A comparative bioavailability study was undertaken between a new formulation of rifampicin 'Famcin' and a standard formulation of rifampicin 'R-cin' in eight healthy male volunteers at two dose levels: 300 mg and 450 mg given orally under both single dose and steady state conditions. Plasma rifampicin was assayed spectrophotometrically. The study documented comparable rate and extent of bioavailability. (Cmax, Tmax and AUC0-infinity) and elimination half-lives (t1/2) of the two brands of rifampicin when compared at similar dose levels. The study establishes the bioequivalence of Famcin to that of the standard brand R-cin. Further, a comparative in vitro microbiological sensitivity of the two brands of rifampicin was undertaken against several strains of two test micro-organism viz. Staphylococcus aureus and Mycobacterium tuberculosis. For both the micro-organisms the minimal inhibitory concentration of Famcin was lower than that of R-cin, suggesting a somewhat greater potency of Famcin in suppressing the growth of test micro-organisms.

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“…To put this into perspective, 50–100% (up to 1-fold) differences in the extent of drug absorption via the oral route are rare [59], e.g. phenytoin [60]or chloramphenicol [61]. The data presented in table 7 show a broad potency range (I–V) of various marketed 0.5% betamethasone dipropionate products.…”

Section: The Vehicle – Pharmaceutical Carrier Of Dermatological Agentsmentioning

confidence: 99%

The Mystical Effects of Dermatological Vehicles

Surber

Smith

2005

Dermatology

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Topical treatment of the skin is as old as the evolution of man. Instinctively, we try to treat a skin injury or irritation with cooling or soothing substances. Even animals lick their wounds, trusting instinctively in the healing power of saliva. When did this archaic pattern of treatment take the gigantic leap from folk medicine to modern drug therapy? This text illustrates the evolution of topical dermatological vehicles, their application (guidelines) and future use. In particular, a phenomenon that has so far been ignored in product development and clinical testing is the vehicle metamorphosis. In clinical and experimental situations, most dermatological vehicles undergo considerable changes after they have been removed from the primary container and are applied to the skin. Subsequently, the initial structural matrix, and the quantitative composition of the vehicle, will most likely change during and after the mechanical shear associated with application of the product and/or evaporation of ingredients. This natural, but highly dynamic process will generate mini-environments for the active moiety that are difficult to predict and that are crucial to the fate of the active moiety. Despite the reasonable wishes of formulators, clinicians, patients and customers, there are still no universal vehicles. Each drug, at each concentration, requires a different vehicle for optimized therapy. Stability and compatibility of excipients and active moiety are crucial for any commercially available pharmaceutical or cosmetic formulation, together with local and systemic safety of all components. Nonetheless, more diverse and molecularly complex classes of new dermatological vehicles are continuously being researched and refined. The scientific progress has been remarkable when one considers the simple emulsion mixtures that were commonplace in dermatological therapy and still persist to this day in commercial products. It is to be hoped that the result of these research endeavors will be the emergence of more innovative topical formulations, applying engineered bioavailability control systems, with broader applications in topical therapeutic and cosmetic vehicles.

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Bioavailability of 11 phenytoin products

Cited by 34 publications

References 6 publications

Is saliva suitable as a biological fluid in relative bioavailability studies? Analysis of its performance in a 4 × 2 replicate crossover design

Is saliva suitable as a biological fluid in relative bioavailability studies? Analysis of its performance in a 4 × 2 replicate crossover design

Comparative bioavailability and in-vitro antimicrobial activity of two different brands of rifampicin

The Mystical Effects of Dermatological Vehicles

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