ABSTRACT
BACKGROUND: The introduction of a new methodology for the pricing of drugs by the Agency of Medicines of the Republic of Macedonia for the period 2012 to 2015 resulted in a price reduction of 1386 drugs. OBJECTIVE: This pioneer study evaluated the effects of the price changes during this period of 4 years and the consequent effects on the sale quantities for the segmented Anatomical Therapeutic Chemical groups. METHODS: The drugs were grouped by the size of the reductions, by segmenting the drugs by generic names, and by the Anatomical Therapeutic Chemical classification, in which the quantities are grouped by generic names and the prices are calculated by average values for a period of 1 year. RESULTS: Analysis of the relations between price changes and quantities sold showed that since the introduction of the new methodology the decrease in the prices pushed down the sales of the drugs. CONCLUSIONS: This article presents not only the market developments but also projects the tendencies, concluding clearly that focusing only on the price reduction of drugs and not on the implementation of the pharmacoeconomic studies is deviating the supply of drugs that are on the market and affecting their quality. The trends indicate that patients are using old-generation drugs, packaging forms that do not fully answer the market demand, and policies that significantly affect the suppliers. The presented analysis confirms that if the new methodology is only partially implemented and is not followed in full consideration of the pharmacoeconomic studies, negative consequences will also have an impact on regional pharmaceutical markets, which are benchmarking prices of drugs with the Macedonian market.
Subject(s)
Drug Costs , Drugs, Generic/economics , Commerce , Cost Control , Costs and Cost Analysis , Drug Industry , Economic Competition , Economics, Pharmaceutical , Europe , HumansABSTRACT
Antipsychotic drugs are widely used in the treatment of schizophrenia and psychotic disorder. The lack of antipsychotic response and treatment-induced side-effects, such as neuroleptic syndrome, polydipsia, metabolic syndrome, weight gain, extrapyramidal symptoms, tardive dyskinesia or prolactin increase, are the two main reasons for non-compliance and increased morbidity in schizophrenic patients. During the past decades intensive research has been done in order to determine the influence of genetic variations on antipsychotics dosage, treatment efficacy and safety. The present work reviews the molecular basis of treatment response of schizophrenia. It highlights the most important findings about the impact of functional polymorphisms in genes coding the CYP450 metabolizing enzymes, ABCB1 transporter gene, dopaminergic and serotonergic drug targets (DRD2, DRD3, DRD4, 5-HT1, 5HT-2A, 5HT-2C, 5HT6) as well as genes responsible for metabolism of neurotransmitters and G signalling pathways (5-HTTLPR, BDNF, COMT, RGS4) and points their role as potential biomarkers in everyday clinical practice. Pharmacogenetic testing has predictive power in the selection of antipsychotic drugs and doses tailored according to the patient's genetic profile. In this perception pharmacogenetics could help in the improvement of treatment response by using different medicinal approaches that would avoid potential adverse effects, reduce stabilization time and will advance the prognosis of schizophrenic patients.
Subject(s)
Antipsychotic Agents/therapeutic use , Cytochrome P-450 Enzyme System/genetics , Psychotic Disorders/drug therapy , Receptors, Dopamine/genetics , Receptors, Serotonin/genetics , Schizophrenia/drug therapy , ATP Binding Cassette Transporter, Subfamily B/genetics , Antipsychotic Agents/adverse effects , Basal Ganglia Diseases/chemically induced , Basal Ganglia Diseases/genetics , Brain-Derived Neurotrophic Factor/genetics , Catechol O-Methyltransferase/genetics , Dyskinesia, Drug-Induced/genetics , Humans , Metabolic Syndrome/chemically induced , Metabolic Syndrome/genetics , Pharmacogenetics , Polymorphism, Genetic , RGS Proteins/genetics , Serotonin Plasma Membrane Transport Proteins/genetics , Treatment Outcome , Weight Gain/geneticsABSTRACT
Following a single oral administration of ciprofloxacin, norfloxacin, pefloxacin and ofloxacin preparations to healthy volunteers simultaneously collected, saliva and plasma 4-fluoroquinolone concentrations were assayed by HPLC. Pharmacokinetic properties were determined by ordinary least squares fitting of the two compartment pharmacokinetic model to the experimental data. A good correlation between plasma and saliva data has been demonstrated. The saliva to venous plasma drug concentration ratio S/P appeared to be time-dependent in the case of norfloxacin and pefloxacin. It was demonstrated that S/P is a function of the quotient of the rate of absorption and venous plasma drug concentration. The calculated S/P ratios with the influence of absorption eliminated, (S/P)(corr) are: ciprofloxacin 0.53+/-0.02, norfloxacin 0.34+/-0.04, ofloxacin 0. 43+/-0.02 and pefloxacin 0.39+/-0.02 (mean+/-S.E.). These values are apparently independent of log D thus making it impossible to predict S/P on the basis of partition principles. The corresponding (S/P)(dif) ratios were calculated on the basis of the assumption that an equilibrium is established across the blood-saliva barrier, which is permeable only for nonionized and nonprotein bound drug fraction. Comparing (S/P)(corr) with the calculated (S/P)(dif) ratios it is evident that 4-fluoroquinolone permeation in saliva cannot be described by passive diffusion based on pH-partition theory.
