Pharmacology research & perspectives
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Our objective was to examine the trends and variation in opioid prescribing in Estonia from 2011 to 2017. This retrospective cross-sectional study is based on a nationwide prescription medicines database. We stratified the analysis by treatment indication (cancer vs noncancer pain). ⋯ The annual number of prescriptions per patient did not change substantially (from 2.94 in 2011 to 2.87 in 2017), and was higher among cancer patients (5.07 vs 2.67 annual prescriptions per cancer and noncancer patients, respectively, in 2017). The use of the most potent opioids (morphine, fentanyl) was higher in noncancer than in cancer patients. The use of prescription opioids is low, and raises concern about the potential undertreatment of cancer pain, in parallel with misuse of opioids for either noncancer pain or diversion.
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Pharmacol Res Perspect · Apr 2020
Population pharmacokinetic and exposure-response analysis of eptinezumab in the treatment of episodic and chronic migraine.
Eptinezumab is a humanized mAb that targets calcitonin gene-related peptide and is under regulatory review for the prevention of episodic and chronic migraine (EM, CM). It is important to determine whether exposures achieved with intravenous (IV) administration of eptinezumab achieve desired pharmacologic effects. Population pharmacokinetics, including dose- and exposure-response analyses, were performed using patient-level data from the eptinezumab clinical trial program with IV doses ranging from 10 to 1000 mg in pharmacokinetic analyses or 10 to 300 mg in phase 2/3 clinical studies in patients with EM or CM. ⋯ A saturable inhibitory Emax model found the exposure over 12 weeks produced by single-dose eptinezumab 100 and 300 mg exceeded the exposure estimates required to achieve 90% of the maximal efficacy (EC90 ). This pharmacokinetic analysis of eptinezumab supports dosing every 12 weeks with no adjustment for patient characteristics, including exposures associated with 100- or 300-mg doses producing optimal efficacy effects. The similar efficacy profiles support 100 mg as the lowest effective dose of eptinezumab.
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Pharmacol Res Perspect · Apr 2020
Differential activation of G protein-mediated signaling by synthetic cannabinoid receptor agonists.
Synthetic cannabinoid receptor agonists (SCRAs) are new psychoactive substances associated with acute intoxication and even death. However, the molecular mechanisms through which SCRAs may exert their toxic effects remain unclear-including the potential differential activation of G protein subtypes by cannabinoid receptor type 1 (CB1), a major target of SCRA. We measured CB1-mediated activation of Gαs and Gαi/o proteins by SCRAs by examining stimulation (pertussis toxin, PTX treated) as well as inhibition (non-PTX treated) of forskolin (FSK)-induced cyclic adenosine monophosphate (cAMP) accumulation in human embryonic kidney (HEK) cells stably expressing CB1. ⋯ By contrast, the potency of SCRAs for inhibition of cAMP (Gαi/o ) was 5F-MDMB-PICA > AB-FUBINACA > PB-22 > JWH-018 > XLR-11. The different rank order of potency and EMax of the SCRAs to stimulate Gαs -like signaling compared to Gαi/o signaling suggests differences in G protein preference between SCRAs. Understanding the apparent differences among these drugs may contribute to unravelling their complex effects in humans.
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Pharmacol Res Perspect · Apr 2020
Retrospective assessment of acute poisoning incidents by pharmaceutical agents in Jordan: Data from Pharmacy One™ Poison Call Center, 2014 to 2018-Part II.
Poison control centers provide surveillance data that can be used to estimate the magnitude of poisoning cases and the level of public awareness and to evaluate control measures. The aim of this study is to describe the drug-related poisoning queries received by the Pharmacy One™ Poisoning Call Center (P1 PCC) in Jordan. This is a retrospective descriptive study of the acute drug-related poisoning incidents in the Jordanian population recorded by the P1 PCC during the 2014-2018 period. ⋯ Poisoning incidents were mainly classified as mild to moderate (56.1%), while only 16.6% were severe. The P1 PCC has demonstrated an important and vital role in improving patient safety and providing education on rational drug use. Reflections on these data can be used to increase public awareness in promoting the rational use of medications among Jordanian citizens.