Stereoselective Pharmacokinetics of Ketoprofen After Oral Administration of Modified-Release Formulations in Caucasian Healthy Subjects

Lorier, Marianela; Magallanes, Laura; Ibarra, Manuel; Guevara, Natalia; Vázquez, Marta; Fagiolino, Pietro

doi:10.1007/s13318-015-0313-2

Cited by 19 publications

(12 citation statements)

References 21 publications

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“…Subsequent research by the same group found that expectation of analgesia in men was the likely reason for the difference in ibuprofen efficacy in this model (Butcher and Carmody, 2012). The absorption of ketoprofen is more rapid in men than in women, with men achieving higher maximum concentrations in the plasma (Lorier et al, 2016;Magallanes et al, 2016); however, this NSAID is not as commonly used for acute migraine treatment. Not all NSAIDs show a sex-related difference in their PK.…”

Section: Nsaidsmentioning

confidence: 88%

Sex-Specific Pharmacotherapy for Migraine: A Narrative Review

Gazerani

Cairns

2020

Front. Neurosci.

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Migraine is a common neurological disorder characterized by recurrent headache episodes that accompany sensory-motor disturbances, such as higher sensitivity to touch and light, extremity heaviness or weakness, and speech or language disabilities. Worldwide, migraine is one of the top 10 causes of disability and hence poses a huge economic burden to society. On average, migraine occurs in 12% of population but its occurrence is sexually dimorphic, as it is two to three times more prevalent in women than in men. This female to male ratio of migraine prevalence is age-and sex hormone-dependent. Advancements in understanding migraine pathogenesis have also revealed an association with both genetics and epigenetics. The severity of migraine, in terms of its attack duration, headache intensity, frequency, and occurrence of migraineassociated symptoms, has generally been reported to be greater in women. Sex differences in migraine disability and comorbidities, such as psychiatric disorders, have also been noted in some population-based studies. However, research on sex-related differences in response to migraine treatments is relatively scarce. Although a general observation is that women consume more medication than men for migraine treatment, strategies for the use of abortive and preventive medications for migraine are generally similar in both sexes. This narrative review summarizes available findings on sexually distinct responses to abortive and prophylactic pharmacotherapy of migraine. Basic experimental data and clinical findings will be presented, and potential mechanisms underlying sex-based responses will be discussed to highlight the importance and value of sex-based treatment in migraine research and practice.

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Section: Nsaidsmentioning

confidence: 88%

Sex-Specific Pharmacotherapy for Migraine: A Narrative Review

Gazerani

Cairns

2020

Front. Neurosci.

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“…Once in the duodenum, the accumulated drug in the pancreatic juice is available for reabsorption, resulting in a perceptible multiple peak plasma concentration-time proile. This phenomenon was evidenced by our group in a study carried out in healthy volunteers after ketoprofen administration [6]. In this work, no evidence of secondary peaks was obtained, probably because of the small amount of drug in blood, but once the reabsorption of ketoprofen took place, after the ingestion of food, signiicant R-to S-isomers conversion could be detected.…”

Section: Nsaids and Acetaminophenmentioning

confidence: 48%

Pharmacotherapy of Chronic Pain

Vázquez¹,

Fagiolino²

2017

Pain Relief - From Analgesics to Alternative Therapies

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In the past two decades, many preclinical works have been carried out assisting in our understanding of the underlying pathophysiological mechanisms that cause chronic pain. Chronic pain involves multiple pathophysiological mechanisms with peripheral and central components. This research in basic and clinical research has greatly expanded the options for analgesic pharmacotherapy. This chapter gives information regarding the major classes of medication used to assist in the management of chronic pain, including nonopioids analgesics such as NSAIDs and acetaminophen, opioids analgesics, antidepressants and anticonvulsants and an emerging area as the ield of cannabinoids is. Importantly, chronic pain treatment encompasses multiple agents to take advantage of synergistic mechanism of actions, but drug-drug interactions have to be taken into account in order to avoid lack of eicacy or toxicity.

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“…This finding explained the sex-related amount of ketoprofen absorbed from extended release formulations and the recirculation rate of its stereoisomers [15]. According to this, it could be hypothesized that women present a shorter absorption window for furosemide (pKa 3.8, [16]) in comparison with men (vertical line in Figures 4 and 5 represent the limit of time above which the absorption would be negligible, in women and men respectively). For this reason, furosemide could be absorbed to the same extent from both formulations in men.…”

Section: Sex-related Differences In the Gastrointestinal Tractmentioning

confidence: 88%

Sex-related in vitro/in vivo and PK/PD correlations after oral single dose furosemide administration

Magallanes¹,

Fagiolino²,

Vázquez³

et al. 2016

J Pharm Technol Drug Res

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Background: The goal of this study was to develop an in vivo-in vitro (IVIV) correlation, both in men and women, which allows constructing a model to predict bioequivalence assessments for drugs with narrow absorption windows. Besides, pharmacokinetic and pharmacodynamic equivalences were also investigated. Furosemide was chosen as a prototype. Methods: Twelve healthy Caucasian volunteers (8 women and 4 men) participated in a relative bioavailability study. Two oral formulations [Lasix ® (Reference, R) and Furosemide EFA ® (Test, T)] were administered under fasting conditions. Urinary excretion of unchanged drug (PK), and of chloride, sodium and potassium (PD) wasmonitored throughout time. PK and PD parameters were calculated from each respective excretion rate versus time curve. In vitro dissolution testing of both formulations was carried out using the USP apparatus 2 and 4 with fixed and variable dissolution media. Results: T and R could be considered bioequivalent since the 90% confidence intervals for the T/R ratio of geometric means for the area under the urinary drug excretion rate versus time curve and for the maximum excretion rate were within the 0.80-1.25 bioequivalence interval. However, T had faster initial absorption and higher levels in women, while R displayed such characteristics in men. Closer IVIV correlations in women were obtained when apparatus 4 with variable biorelevant dissolution media were used [going from fasting state simulated gastric fluid to fasting state simulated intestinal fluid]. Since R had faster disintegration time than T, a shorter stay of R under gastric conditions was required in order to obtain a good IVIV correlation in men. Saluretic effect displayed a typical clockwise hysteresis loop for the PKPD correlation assessed through chloride-versus-furosemide urinary excretion rates. Even though a higher amount of furosemide was excreted with the urine in men, differences in the excretion of electrolytes between sexes were almost negligible. Conclusions: Sex-differences in the gastrointestinal transit of formulations, under fasting conditions, determined the extent and the rate of furosemide absorption. The prolongation of the absorption process by mean of slowing the gastric emptying would make the formulation more effective. The USP-4 apparatus with variable dissolution media was able to discriminate the formulations even between sexes, becoming a promissory in vitro dissolution testing to predict bioequivalence. Keywords: Furosemide, oral absorption, IVIV and PKPD correlations, sex-by-formulation interaction, bioequivalence © 2016 Fagiolino et al; licensee Herbert Publications Ltd. This is an Open Access article distributed under the terms of Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0). This permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. IntroductionFurosemide is a loop diuretic that is commonly used in the treatment of edematous states associated with car...

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Stereoselective Pharmacokinetics of Ketoprofen After Oral Administration of Modified-Release Formulations in Caucasian Healthy Subjects

Abstract: R-to-S conversion rate could be mainly associated with several passages of the drug through the intestinal mucosa. The concentration-time profiles of ketoprofen in plasma after the administration of both formulations evidenced R-to-S conversion of recirculating drug following meal intakes.

Cited by 19 publications

References 21 publications

Sex-Specific Pharmacotherapy for Migraine: A Narrative Review

Sex-Specific Pharmacotherapy for Migraine: A Narrative Review

Pharmacotherapy of Chronic Pain

Sex-related in vitro/in vivo and PK/PD correlations after oral single dose furosemide administration

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