Parkinson’s disease (PD) is a progressive, neurodegenerative disorder primarily affecting dopaminergic neuronal systems, with impaired motor function as a consequence. The most effective treatment for PD remains the administration of oral levodopa (LD). Long-term LD treatment is frequently associated with motor fluctuations and dyskinesias, which exert a serious impact on a patient’s quality of life. The aim of our study was to determine the pharmacokinetics of LD: used as monotherapy or in combination with ropinirole, in patients with advanced PD. Furthermore, an effect of ropinirole on the pharmacokinetics of 3-OMD (a major LD metabolite) was assessed. We also investigated the correlation between the pharmacokinetic parameters of LD and 3-OMD and the occurrence of motor complications. Twenty-seven patients with idiopathic PD participated in the study. Thirteen patients received both LD and ropinirole, and fourteen administered LD monotherapy. Among 27 patients, twelve experienced fluctuations and/or dyskinesias, whereas fifteen were free of motor complications. Inter- and intra-individual variation in the LD and 3-OMD concentrations were observed. There were no significant differences in the LD and 3-OMD concentrations between the patients treated with a combined therapy of LD and ropinirole, and LD monotherapy. There were no significant differences in the LD concentrations in patients with and without motor complications; however, plasma 3-OMD levels were significantly higher in patients with motor complications. A linear one-compartment pharmacokinetic model with the first-order absorption was adopted for LD and 3-OMD. Only mean exit (residence) time for 3-OMD was significantly shorter in patients treated with ropinirole. Lag time, V/F, CL/F and t_max of LD had significantly lower values in patients with motor complications. On the other hand, AUC were significantly higher in these patients, both for LD and 3-OMD. 3-OMD C_max was significantly higher in patients with motor complications as well. Our results showed that ropinirole does not influence LD or 3-OMD concentrations. Higher 3-OMD levels play a role in inducing motor complications during long-term levodopa therapy.

In the treatment of pain, especially chronic pain, the rule of multimodal therapy applies, based on various painkillers mechanisms of action. The aim of the conducted study was to evaluate the in vitro penetration of ketoprofen (KET) and lidocaine hydrochloride (LH) through the human skin from a vehicle with transdermal properties. The results obtained with the use of the Franz chamber showed statistically significantly higher penetration of KET from the transdermal vehicle as compared to commercial preparations. It was also shown that the addition of LH to the transdermal vehicle did not change the amount of KET permeated. The study also compared the penetration of KET and LH by adding various excipients to the transdermal vehicle. Comparing the cumulative mass of KET that penetrated after the 24-h study, it was observed that the significantly highest permeation was found for the vehicle containing additionally Tinctura capsici, then for that containing camphor and ethanol, and the vehicle containing menthol and ethanol as compared to that containing Pentravan^® alone. A similar tendency was observed in the case of LH, where the addition of Tinctura capsici, menthol and camphor led to a statistically significant higher penetration. Adding certain drugs such as KET and LH to Pentravan^®, and substances such as menthol, camphor or capsaicin, can be an interesting alternative to administered enteral drugs especially in the group of patients with multiple diseases and polypragmasy.

Levodopa remains the main drug in the treatment of patients with Parkinson’s disease. Unfortunately, after several years of levodopa treatment, the response duration to each dose shortens as the disease progresses. The present publication describes a rapid, sensitive and precise high-performance liquid chromatographic method (HPLC) with electrochemical detection for the simultaneous analysis of levodopa and its metabolite 3-O-methyldopa (3-OMD) in plasma in patients with Parkinson’s disease. The HPLC system used in this study consisted of an isocratic pump, electrochemical detector with the conditioning cell and dual-electrode analytical cell operating in redox mode. The separation was achieved with a ThermoHypersil Gold C₁₈ reversed phase column, using 0.1 M potassium phosphate, 0.5 mM EDTA, 20 mg/L 1-octanesulfonic acid sodium salt and 1% acetonitrile as a mobile phase (pH = 3.0). The method was optimized and fully validated by determining precision and accuracy, LOD, LOQ, recovery and stability. This method was successfully used in pharmacokinetic studies in 14 patients with Parkinson’s disease after oral administration 100 mg levodopa and 25 mg benserazide or 100 mg levodopa and 25 mg carbidopa. Our method is suitable for levodopa therapy monitoring and for investigating the pharmackonietics of the drug in patients with Parkinson’s disease.

Background and objective: Clopidogrel is frequently used as part of optimal dual antiplatelet therapy in high-bleeding risk patients with the acute coronary syndrome. The concentration of the inactive carboxylic acid metabolite of clopidogrel might be useful to evaluate the response to clopidogrel therapy. Therefore, we sought to correlate the inhibition of platelet aggregation with the plasma level of the inactive metabolite of clopidogrel in patients after percutaneous coronary interventions (PCI) and their associations with the most frequently studied genetic polymorphisms. For this purpose, the fast and simple HPLC method for determining the concentration of the inactive metabolite was developed. Methods: The effect of CYP2C19, CYP3A4/5, ABCB1 and PON1 genes on the plasma inactive metabolite concentration of clopidogrel and the platelet aggregation was investigated in 155 patients before and after PCI. Results: The concentration of the inactive metabolite of clopidogrel was not significantly different in the intermediate metabolizers (IM) of CYP2C19 compared with extensive metabolizers (EM) both before and after PCI, while inhibition of platelet aggregation was found to be significantly better in EM than in IM. The presence of the A allele at position 2677 in the ABCB1 gene was associated with a significantly lower concentration of inactive metabolite of clopidogrel before PCI. Conclusion: The CYP2C19*2 allele was associated with decreased platelet reactivity during clopidogrel therapy before and after PCI. Simultaneous determination of platelet aggregation and concentration of the inactive clopidogrel metabolite may be useful in clinical practice to find the cause of adverse effects or insufficient treatment effect in patients chronically treated with clopidogrel.

Background/Objectives: This study aimed to evaluate the degradation of omeprazole suspension under various pH conditions and to propose recommendations for preparing compounded suspensions. Given the clinical need for alternative dosage forms for pediatric and geriatric patients and those with dysphagia, the research focused on assessing whether modifications in formulation composition—specifically the inclusion of sodium bicarbonate—could improve omeprazole stability, thus enhancing its bioavailability. Methods: Three formulations were prepared: O1, based on crushed enteric-coated pellets from a commercial product; O2, with crushed pellets suspended in an 8% sodium bicarbonate solution with glycerin; and O3, with pure omeprazole suspended in an 8% sodium bicarbonate solution with glycerin. Release studies were conducted using basket or paddle apparatus under conditions simulating fasted (pH 1.2 and 6.8) and fed (pH 6, 4.5, and 3) gastric and intestinal juices at 37 °C over 120 min. At predetermined intervals, samples were withdrawn and analyzed by a validated HPLC method with UV detection to quantify the released omeprazole. Results: The commercial enteric-coated product showed no release at a low pH, confirming its protective coating. In contrast, formulation exhibited significant degradation in acidic environments. The O2 formulation, benefiting from the buffering effect of sodium bicarbonate, showed improved stability compared to O1. Notably, formulation O3 yielded the highest drug recovery, with approximately 74% released at pH 6 and 65% at pH 6.8, demonstrating significantly better performance, as confirmed by statistical analysis (p < 0.05). Conclusions: The composition of omeprazole suspensions substantially influences the drug stability and release profiles. The O3 formulation, based on pure omeprazole with sodium bicarbonate, is recommended for immediate-release suspensions to enhance bioavailability. Further studies are needed to optimize conditions for pediatric use.