Lipophilicity Descriptors Correlate Uniquely with Pharmacokinetic and Blood-Brain Barrier Penetration Parameters for Selected Antipsychotic Drugs

Lipophilicity is an important physicochemical parameter of biological relevance; although its in- vivo predictive capability is dependent on accuracy and reliability of platforms used for its determination. This work examines biomimetic attribute of isocratic chromatographic hydrophobicity index (ICHI), experimental logarithm of octanol ­ water partition coefficient (LogP) and some computed lipophilicity indices for eight (8) selected antipsychotic agents and their predictive capability in drug discovery. The retention behavior of 5 first-generation and 3 second-generation antipsychotics was determined on reversed-phase chromatographic platform using methanol-phosphate buffer (pH 6.8) mobile phase. The retardation factor obtained was transformed to Rm, and plotted against volume fraction of organic modifier in the mobile phase to generate linear graph whose x- intercept is ICHI. Experimental LogP values were curled from literature while computed LogP were obtained using respective software. The experimentally determined LogPoctanol/water and ICHI were first correlated with index of brain permeability (BBB); before all lipophilicity indices were comparatively evaluated and correlated with in-vivo-normalized pharmacokinetic parameters curled from literature. ICHI gave better correlation with BBB index (r = 0.976) compared to Log Poctanol/water (r = 0.557). Comparative lipophilicity evaluation shows clustered pattern for second generation antipsychotics compared to first generation. In vivo correlation was poorer for the 8 drugs (r < 0.7), better with subset of phenothiazine homologues (r = 0.51 to 0.97). The ALogP, LogPoctanol/water, cLogP and ICHI gave highest correlation with the pharmacokinetic parameters. The biomimetic attributes of ICHI is better than for LogPoctanol/water in predicting brain permeability, but lower for in-vivo pharmacokinetic prediction.

Studies and evaluation of compressed microspheres

This work was aimed at the use of dissolution testing and similarity factor to assess the level of damage taken by active drug microspheres during compression in tablet dosage form. To achieve that, combinations of suitable excipients were used to protect drug microspheres during compression. The excipients were used in the form of powders, granules or placebo pellets prepared by extrusion-spheronization technology. The excipients were evaluated alone, in combinations and post-compression into compacts. Preliminary experiments included density, hardness, friability and disintegration on all of the selected excipients. Based on such experiments it was found that the flowability of combination powders was more acceptable than individual excipients. Two combinations of microcrystalline -starch and microcrystalline cellulose -calcium carbonate granules were selected to be compressed with active ketoprofen pellets. In all the combinations used there was a significant amount of damage to drug pellets. The kinetics of drug release appears to follow the zero-order rate and the rate remained unchanged even when a significant degree of damage to pellets occur. It was found that a high level of excipients is required in order to prepare microspheres as a rapid disintegrating tablet

Drug Interactions in Primary Health Care in the George Subdistrict; South Africa: a Cross-Sectional Study

Objectives: To investigate the prevalence of potential drug-drug interactions in primary healthcare clinics in the George subdistrict; to determine which drugs were involved; and to identify associated risk factors. Design: A cross-sectional retrospective folder review was performed.Setting and subjects: Four hundred randomly selected patient files from four primary care clinics in the George subdistrict. Outcome measures: The prevalence of potential drug-drug interactions in primary care; drugs involved in potential drug-drug interactions and associated risk factors. Results: The prevalence of scripts containing at least one moderate potential interaction was 42; severe potential interaction; 5.25; and contraindicated combinations; 0.5. The most common drugs involved were enalapril; aspirin; ibuprofen; furosemide and fluoxetine. The most common implicated drugs in potentially severe interactions were warfarin; aspirin; fluoxetine; tramadol and allopurinol. Two contraindicated combinations were found; namely verapamil plus simvastatin; and hyoscine butyl bromide plus oral potassium chloride. Advancing age and polypharmacy were associated with an increased risk of potential drug-drug interactions. Input from the regional hospital specialist departments greatly increased the risk of a patient being given a prescription that contained a potential drug-drug interaction. Eighty one per cent of severe interactions were from this group. Conclusion: The potential for drug-drug interactions occurring was common in primary healthcare clinics in the George subdistrict. Drug interactions are predictable and preventable. The risk factors identified in this study may assist in the design of interventions that reduce the risk

Pharmaceutical Equivalence of Some Commercial Samples of Artesunate and Amodiaquine Tablets Sold in Southwestern Nigeria

Purpose: To study the physical properties and dissolution profiles of commercial samples of artesunate and amodiaquine tablets. Methods: Fifteen generic brands of artesunate and five generic brands of amodiaquine tablets were obtained from drug retail outlets in Oyo and Ogun States in southwestern Nigeria. The tablets were subjected to various compendial tests including identification; weight uniformity; uniformity of content; content of active ingredient and uniformity of diameter. Additional tests used as a basis for the assessment of the pharmaceutical equivalence of the products include hardness; disintegration time and dissolution rate. Data obtained were analysed by correlation analysis; Chi-square and ANOVA. Results: Thirteen generic brands of artesunate (87) and four amodiaquine brands (80) investigated were imported. Two brands of the imported artesunate brands were found to contain undetectable amount of artesunate while another 8 samples contained overages. All the amodiaquine brands passed the assay test as stipulated by United States Pharmacopoeia (USP) for amodiaquine tablets while tablet disintegration time of amodiaquine products ranged from 5.8 - 20.7 min. All but one artesunate sample passed the disintegration test too. A majority of the artesunate brands tested had significantly different dissolution profiles (p 0.05). Four (80) of the amodiaquine tablet brands tested had similar dissolution profiles and percent drug released within 30 min (p 0.05). One amodiaquine brand demonstrated poor dissolution profile as it did not meet minimum dissolution requirements within 30 min. Conclusion: The detection of substandard artesunate tablets and a poorly formulated amodiaquine tablet amongst the few sample brands studied highlights the need for increased drug surveillance and monitoring of the qualities of antimalarial medicines currently in use in order to prevent widespread treatment failure

Review: Strategies for the Prevention and Containment of Antibiotic Resistance

Antibiotic resistance may emerge by antibiotic selection pressure but is perpetuated by diverse risk factors and maintained within environments as a result of poor infection control. Population-specific drug pharmacokinetics and pharmacodynamics also play a role. The WHO; US; UK and EU have initiated strategies for the containment of resistance; with surveillance and delineation of the cause(s) cited as essential. Surveillance of antibiotic efficacy should be disease-based; establishing sensitivity profiles of common causative organisms to inform the development of or amendment to standard treatment guidelines and essential drugs lists adopted within the national drug policy. The manner of antimicrobial use (overuse; underuse; inadequate dosing) associated with resistance should be established for appropriate intervention in terms of rational drug use; a reduction in use and dosing regimens based on population-specific pharmacokinetics and pharmacodynamics. Risk factors unique to South African communities (poverty; HIV) and hospitals (duration of hospitalisation; location within the hospital; intensive care unit stay; surgery; wounds; previous and current antimicrobial therapy; mechanical ventilation; urinary catherterisation; nasogastric intubation; central venous and peripheral catheters; previous hospitalisation and transfer from another unit or hospital) must be determined and due vigilance exercised in patients exhibiting classical risk factors for the acquisition of or colonisation with resistant pathogens. Hygiene and sanitation (in communities) and infection control (in hospitals) status must be determined and interventions initiated to prevent the spread of resistance. Pharmacokinetics and pharmacodynamics specific to diverse populations must be devised to optimise antimicrobial therapy. South Africa has unique needs in the antimicrobial resistance arena; needs to be addressed in the context of severe financial; human resources and technological challenges

Compression, mechanical and release properties of chloroquine phosphate tablets containing corn and trifoliate yam starches as binders

PURPOSE : A study was made of the binding properties of trifoliate yam starch; obtained from Dioscorea dumetorum (Pax); in chloroquine phosphate tablet formulations in comparison with official corn starch. METHOD: Compressional properties were analyzed using density measurements and compression equations of Heckel and Kawakita. The mechanical properties of the tablets were assessed using the crushing strength and friability of the tablets; while drug release properties of the tablets were assessed using disintegration and dissolution times. RESULTS : Tablet formulations containing trifoliate yam starch exhibited faster onset and higher amount of plastic deformation during compression than those containing corn starch. The crushing strength; disintegration and dissolution times of the tablets increased with binder concentration while friability values decreased. Trifoliate yam starch produced tablets with stronger mechanical properties and longer disintegration and dissolution times than those containing corn starch. CONCLUSION : Trifoliate yam starch would be a better alternative to corn starch in producing uncoated tablets for which high bond strength is essential

Pharmacologie de l'Insuline

La structure de l'insuline est connue et decrite. Les principes de la fabrication sont rappeles brievement. Le dosage immunologique est indispensable a toute etude in vitro. Il valut le prix Nobel a ses savants. Nous rappelons egalement la composition des differents types d'insuline; rapide ou retardee. L'insuline humaine est fabriquee d'une part par genie genetique et de l'autre par genie chimique. Diverses insulines sont mises dernierement sur le marche pour mimer de plus pres la secretion physiologique. L'insuline peut causer la presence d'anticorps de type divers

Pharmacokinetics and tissue responsiveness in neonates

"Neonates and infants are not just ""little humans"". Pharmacologically and in therapeutic considerations; empirical rules for dosage adjustments for children are still useful guidelines; but; sometimes; it is equally important to take other factors besides age; body weight; and body surface areas; (namely: pharmacokinetic parameters; drug intake via breast milk; and tissue responsiveness) into account for fixing drug doses for the neonates."

The bioavailability of chloroquine in healthy adult volunteers

It is recommended that for individuals weighting 45 to 55kg a dose of chloroquine of 600mg on first day 300mg on second day and 150mg on third day would give desired therapeutic non-toxic levels whereas for heavier individuals (80-90kg) the appropriate dosage would be 5 tablets (750mg) first day; 4 tablets (600mg) second day and 3 tablets (450mg) on third day