Development of Dioctyl Phthalate@Fe3O4 Nanocomposite Reinforced Hollow Fiber Solid/ Liquid Phase Microextraction Followed by HPLC-DAD for the Determination of Atorvastatin and Gemfibrozil in Human Urine

Background: The desirable levels of lipids, especially in patients with coronary artery disease, might not be achievable with a single lipid-lowering drug; thus, combination therapy using atorvastatin and gemfibrozil seems to be a promising approach. However, the potential for drug-drug interaction needs to be taken into consideration, and the combination (atorvastatin and gemfibrozil) is recommended only when other options for reducing lipids have been exhausted. Objectives: Many studies are conducted for the determination of atorvastatin or gemfibrozil in biological fluids and tablets; however, the simultaneous determination of the two drugs in complex biological matrices is limited. Consequently, the development of a sensitive method for simultaneous determination of atorvastatin and gemfibrozil in urine samples is urgently needed to make sure that the doses of both medications are given to patients correctly to prevent the risk of side effects outcomes associated with the adverse drug-drug interaction. Methods: A synthesized nanocomposite sorbent, dioctyl phthalate coated on the surface of magnetite (DOP@Fe3O4), was reinforced and immobilized into the pores of 2.5 cm segment hollow fiber microtube via ultrasonication, and the lumen of the microtube was filled with 1-octanol as an organic solvent with two ends heat-sealed. The prepared (DOP@Fe3O4-HF-SLPME) device was directly immersed into 10 mL of a sample solution containing atorvastatin and gemfibrozil with agitation. Subsequently, the microextraction device was transferred to HPLC-micro-vial containing an appropriate solvent, and the selected analytes were desorbed under ultrasonication prior to HPLC-DAD analysis. The main factors influencing the adsorption and desorption process of the selected drugs have been optimized. Results: The DOP@Fe3O4-HF-SLPME combined with the HPLC-DAD method was analytically evaluated for the simultaneous determination of atorvastatin and gemfibrozil in human urine samples using the optimized conditions. In spiked urine samples, the method showed a good linearity R2˃ 0.998, RSD from 1.41- 5.33%, and the limits of detection/ quantification (LOD/ LOQ) were 0.11/ 0.36 and 0.73/ 2.42 µg L-1 for atorvastatin and gemfibrozil, respectively. The enrichment factors of atorvastatin and gemfibrozil were 83.4 and 101.2, with extraction recoveries of 80.9% and 99.0%, respectively. The developed method demonstrated comparable results against referenced methods and a satisfactory result for determining the selected drugs in the patient’s urine samples. Conclusion: The DOP@Fe3O4-HF-SLPME followed by HPLC-DAD was proved to be an efficient, sensitive, and cost-effective biopharmaceutical analysis method for trace levels of atorvastatin and gemfibrozil in the biological fluid matrix.

Reduction of drug-drug interaction and inappropriate prescription in polymedicated elderly who consult in the ambulatory

Introduction: Older adults or elderly people over 64 years of age are patients more vulnerable to suffering adverse events related to medication, and this can generate states of both physical and psychological discomfort, loss of autonomy, mental disorders, etc. Objectives: To analyze the drug-drug interaction and inappropriate prescription of drugs in the outpatient setting in the elderly and implement barriers to reduce this problem. Materials and methods: Quasi-experimental study, of the before after type. The Beers 2019 criteria were used to assess inappropriate drug prescribing. The Uptodate definition of drug-drug interactions and their classification were used. Results: 203 polypathological, sarcopenic elderly patients were studied. These patients attended the outpatient consultation during the 2016-2018 period. 99 patients participated in the pre-intervention and 104 in the post-intervention. The distribution by sex was: 110 (54.2%) women and 93 (45.8%) men. The mean age was 77.3 + 13.3 years. In the total sample analyzed before the intervention, 33 (33.3%) showed inappropriate prescription of drugs criteria. Drug interactions in the pre-intervention were present in 51 patients (51.5%). After the intervention that consisted of training doctors with the Beers criteria and editing a list with clinically relevant interactions in the elderly, which can cause adverse events, inappropriate prescription was reduced to 26 patients (25%), p = 0.05, and clinically relevant interactions were reduced from 51 (51.51%) to 12 (11.53%), p = 0.003. The association between inappropriate prescription and clinically relevant interactions is OR: 3.23 (95% CI 1.91-3.88). Conclusions: The proportion of patients with inappropriate prescription is within the ranges published by various authors as well as drug interactions, the intervention was good to reduce the two problems in this sample of patients.

Drug-Drug Interaction Between Orally Administered Hydrocodone-Acetaminophen and Inhalation of Cannabis Smoke: A Case Report

Objective: To determine if a 2-day protocol measuring pharmacokinetic and pharmacodynamic characteristics can demonstrate drug-drug interactions when smoked cannabis is added to orally administered hydrocodone/acetaminophen combination products. Case Summary: A 51-year-old non-Hispanic white male with chronic pain diagnoses participated in a 2-day pilot protocol. The participant attended two 7-hour in-lab days where he received 10 blood draws each day and completed self-administered pain and anxiety surveys. For both days, the participant took his prescribed dose of hydrocodone/acetaminophen (1/2 tablet of 7.5 mg/325 mg combination product) with the addition of 1 smoked pre-rolled marijuana cigarette (labeled as 0.5 g; 22.17% Δ9-tetrahydrocannabinol; 0.12% cannabidiol) on Day 2. Blood specimens were analyzed using mass spectrometry to quantify the difference of plasma hydrocodone levels between Day 1 and Day 2. Results: Compared to Day 1, lower levels of pain and anxiety were reported during Day 2 with the addition of cannabis to oral hydrocodone/acetaminophen. Day 2 pharmacokinetic analysis also revealed more rapid absorption and overall lower levels of hydrocodone in plasma. Discussion: Lower hydrocodone plasma levels in Day 2 may indicate cannabis’s effect on metabolism and reduce the risk of opioid toxicity. The quicker absorption rate of hydrocodone could explain lower pain and anxiety scores reported on the second day. Conclusion and Relevance: A 2-day protocol was able to capture differences across time in pharmacokinetic and pharmacodynamic measurements. Larger studies can be designed to better characterize the potential drug-drug interaction of cannabis and opioids.