Perception and attitude of physicians toward local generic medicines in Saudi Arabia: A questionnaire-based study

AbstractObjectives: The current study aimed to explore the knowledge, perception, and attitude of physicians toward generic medicines in Saudi Arabia.Background: The local market of generic medicine share in Saudi Arabia is low compared to global and regional statistics. The reason for this low market share and the role of physicians has not previously been investigated. The purpose of this study was to assess health practitioner level of perceived knowledge, opinions and attitudes about local generic medication, and identify factors that influence infrequency of generic prescriptions.Methods: A random sample of 231 physicians was recruited from two hospitals in Riyadh (one government one private) and 178 (77%) responded. Information on the physicians’ perceived knowledge, opinions and attitude toward local generic medication was extracted, analyzed and interpreted. Factors that influence infrequent prescription of local generic drugs were identified.Results: Among the 178 participants in the physicians’ survey, 76% and 47% reported that they are knowledgeable about the terms “generic” and “bioequivalence” respectively, while 44% reported that they are able to explain bioequivalence to their patients. Approximately 52% of physicians reported that local generics should be substituted for brands if suitable for the case, and 21.9% reported that they believe SFDA approved local generics are therapeutically equivalent to their brands. Clinical effectiveness was reported by 71.9% of physicians as the most influential factor effecting prescription of brand over local generic medication. The three independent significant predictors for infrequent prescription of local generics among physicians: Government sector employment (OR=3.74, [95%CI 1.50–9.43]), consultant level (OR=3.94, [95%CI 1.50–10.31]) and low level of knowledge about local generics (OR=4.11, [95%CI 1.56–10.84]).Conclusion: The low market share of local generics medicines attributed to low prescription rates is significantly more among senior-level physicians working in governmental hospitals. Low level of knowledge about generic drugs among physicians was the strongest predictive factor for low prescription. Future bigger studies are needed to confirm these results

An accurate and precise high-performance liquid chromatography method for the rapid quantification of the novel HIV integrase inhibitor raltegravir in human blood plasma after solid phase extraction

The quantification of the HIV integrase inhibitor raltegravir in blood plasma is described using solid phase extraction (SPE) coupled with an accurate high-performance liquid chromatography assay with ultraviolet (UV) detection. The method was validated over the range of 20–10,000ng/mL using simple sample preparation and chromatography. The SPE method was optimized to be selective and highly efficient. The buffer’s ionic strength and pH were optimized for retaining RAL and the internal standard on the column, the percentage of methanol was optimized in the cleaning step to remove unwanted plasma contaminants, and the type and amount of acid was optimized for complete elution of the compounds. This method has no interference with other potentially co-administered antiretrovirals or common drugs. Average recoveries for the extraction method were consistently high: 90% for raltegravir and 90% for the internal standard diazepam. This method was found to be accurate and precise. Within day (n=6) and between day (n=18) accuracies ranged from 97.5% to 104.4%. Within-day (n=6) and between-day (n=18) precision ranged from 1.4% to 3.8%, and from 2.4% to 7.9%, respectively. This is the first published method to use simple UV technology and reliable SPE extraction methodology for the quantification of raltegravir in human plasma. This method can be easily implemented in most bioanalytical laboratories

Quantifying the HIV-1 integrase inhibitor raltegravir in female genital tract secretions using high-performance liquid chromatography with ultraviolet detection

Understanding the pharmacokinetics of drugs in peripheral body compartments, such as the genital tract, is particularly important in the infectious diseases arena. However, extracting drugs from small volumes of viscous, proteinacious substances like cervicovaginal fluid is particularly challenging. The goal of this study was to develop a method to quantify raltegravir, an HIV-1 integrase inhibitor, in the female genital tract. The method included sample preparation with perchloric acid followed by solid-phase extraction, separation with reverse-phase high-performance liquid chromatography, and detection with an ultraviolet wavelength of 218 nm. The method was linear from 0.05 to 10.0 mg/L, with minimal endogenous interference. The method was accurate (1.2–11.0% deviation) and precise (1.1–12.6% CV) for both within and between-day analyses. The ability to detect raltegravir in the female genital tract is essential for future investigations of raltegravir as an agent for prevention of HIV acquisition, and this method will be used for clinical studies further evaluating pharmacokinetic–pharmacodynamic relationships in this body compartment

A novel LC–ESI-MS method for the simultaneous determination of etravirine, darunavir and ritonavir in human blood plasma

The new potent combination of antiretrovirals etravirine, darunavir, and ritonavir requires a new bioanalytical method for clinical pharmacology investigations and potential therapeutic drug monitoring. The development and validation of a novel LC–MS method for the simultaneous quantification of the most recently FDA-approved protease inhibitor and non-nucleoside reverse transcriptase inhibitor is described. This novel method was developed and validated using a sub-2 μm particle column, and provides excellent chromatographic separation and peak shape for all three analytes and internal standard. The method was validated over the range of 0.002–2.0 μg/mL. Intra- and inter-day accuracy of all analytes ranged from 88 to 106%, and intra- and inter-day precision was <7%. Dilution of samples 2-, 5-, and 10-fold maintained accuracy and precision, using a sample volume as low as 10 μL. Finally, the applicability of the method was investigated with clinical samples and external quality assurance proficiency testing samples

Studies on Antiretroviral Drug Concentrations in Breast Milk: Validation of a Liquid Chromatography-Tandem Mass Spectrometric Method for the Determination of 7 Anti-Human Immunodeficiency Virus Medications

Studying the pharmacokinetics of antiretroviral drugs in breast milk has important implications for the health of both the mother and the infant, particularly in resource-poor countries. Breast milk is a highly complex biological matrix, yet it is necessary to develop and validate methods in this matrix, which simultaneously measure multiple analytes, as women may be taking any number of drug combinations to combat human immunodeficiency virus infection. Here, we report a novel extraction method coupled to high-performance liquid chromatography and tandem mass spectrometry for the accurate, precise, and specific measurement of 7 antiretroviral drugs currently prescribed to infected mothers. Using 200 µL of human breast milk, simultaneous quantification of lamivudine (3TC), stavudine (d4T), zidovudine (ZDV), nevirapine (NVP), nelfinavir (NFV), ritonavir, and lopinavir was validated over the range of 10–10,000 ng/mL. Intraday accuracy and precision for all analytes were 99.3% and 5.0 %, respectively. Interday accuracy and precision were 99.4 % and 7.8%, respectively. Cross-assay validation with UV detection was performed using clinical breast milk samples, and the results of the 2 assays were in good agreement (P = 0.0001, r = 0.97). Breast milk to plasma concentration ratios for the different antiretroviral drugs were determined as follows: 3TC = 2.96, d4T = 1.73, ZDV = 1.17, NVP = 0.82, and NFV = 0.21

CYP2B6 Variants and Plasma Efavirenz Concentrations during Antiretroviral Therapy in Port‐au‐Prince, Haiti

Polymorphisms in CYP2B6 are known to predict increased steady-state plasma concentrations of efavirenz. We characterized relationships between genetic polymorphisms and plasma efavirenz concentrations among 45 Haitians who initiated antiretroviral therapy in Port-au-Prince

Plasma Bile Acid Concentrations in Patients with Human Immunodeficiency Virus Infection Receiving Protease Inhibitor Therapy: Possible Implications for Hepatotoxicity

To evaluate whether patients with human immunodeficiency virus (HIV) infection who were receiving protease inhibitor therapy had altered bile acid concentrations compared with noninfected control subjects, and whether bile acid concentrations could predict the onset of hepatotoxicity caused by protease inhibitors

Pharmacokinetics of generic and trade formulations of lamivudine, stavudine and nevirapine in HIV-infected Malawian children

Evaluate the pharmacokinetics (PK) of lamivudine (3TC), stavudine (d4T), and nevirapine (NVP) in HIV-infected Malawian children receiving quartered tablet multiples of Triomune 40™ (GT) compared to individual generic (GL) and trade (TL) liquid

Prevention of SIV Rectal Transmission and Priming of T Cell Responses in Macaques after Local Pre-exposure Application of Tenofovir Gel

Martin Cranage and colleagues find that topical tenofovir gel can protect against rectal challenge with SIV in a macaque model, and can permit the induction of SIV-specific T cell responses

Antiretroviral drug exposure in the female genital tract: implications for oral pre- and post-exposure prophylaxis

To describe first dose and steady state antiretroviral drug exposure in the female genital tract