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Biochemistry
Published in Michael McGhee, A Guide to Laboratory Investigations, 2019
Abnormal test resultsAST levels are markedly raised after: myocardial infarction (MI)cardiac surgery.AST levels are raised in: viral or toxic hepatitismalignancysome skeletal muscle diseasestrauma.Raised ALT, in the presence of raised ALP and with signs or symptoms of liver disease such as spider naevi, palmar erythema, hepatosplenomegaly, bruising or gynaecomastia: REFER IMMEDIATELY.Raised ALT - consider: obesitydiabetesthyroid diseasedrugs, especially statins, some antibiotics, non-steroidal anti-inflammatory drugs (NSAIDs) and sulphonylureas, e.g. glibenclamide, gliclazide, glimepiride, glipizide, gliquidone and tolbutamide.Senna, some herbal remedies and some illicit drugs such as ecstasy can also cause an isolated raised ALT.Small rises in ALT are often seen after initiation of statins and often return to normal.If ALT is three times the upper range of normal after initiation of statin, STOP STATIN.ALT up to twice the normal limit, assess patient for signs of liver disease AND risk factors; repeat LFTs in 3 months and refer if ALT remains high.ALT is low in: renal failurevitamin B6 deficiency.
The role of sulfonylureas in the treatment of type 2 diabetes
Published in Expert Opinion on Pharmacotherapy, 2022
Brian Tomlinson, Nivritti Gajanan Patil, Manson Fok, Paul Chan, Christopher Wai Kei Lam
Gliclazide does not have active metabolites and can be used without dose modification in T2D with stage 1–3 CKD (eGFR > 30 mL/min per 1.73 m2) and in reduced doses in patients with severe CKD [108]. Similarly, glipizide is mainly eliminated by renal excretion of inactive metabolites and can be used in normal doses in mild or moderate renal impairment and in reduced doses when eGFR is <30 mL/min per 1.73 m2 [108]. Gliquidone is rapidly eliminated by hepatic metabolism and does not accumulate in renal impairment [108]. It was suggested it might be the preferred sulfonylurea for patients with mild to moderate renal insufficiency [109].
All-cause and cardiovascular mortality associated with sulphonylurea and metformin therapy in type 2 diabetes
Published in Endocrine Research, 2018
Sorin Ioacara, Cristian Guja, Aura Reghina, Sorina Martin, Anca Sirbu, Simona Fica
Prescription time and dose was accounted for MET, gliclazide, glipizide, gliquidone, glimepiride, and glibenclamide, as time-dependent variables. Exposure during follow-up was calculated in a time-dependent manner separately for MET monotherapy, SU monotherapy, SU added to MET, and MET added to SU. SU added to MET as used in results means combined treatment with SU and MET in a patient with MET monotherapy at screening (and baseline), and likewise for MET added to SU. Combined therapy status was captured in a time-dependent manner, with daily updates of the system. SU replacing MET was used in results for designating patients on SU monotherapy with initial screening allocation to MET group. A sensitivity analysis was done including the above mentioned subclasses of SU. Defined daily dose expresses the average dose of a specific drug as used in the routine clinical practice.11 There was a high heterogeneity of dose exposure expressed in grams, as clearly 1 g of MET cannot be directly compared with 1 g of the available SU. Therefore, individual dose registrations were divided by the corresponding defined daily dose as recommended by the WHO.11 The defined daily dose for gliclazide was 60 mg, resulting in a value of 2 if the patient took a total daily dose of 120 mg. Cumulative dose should be interpreted as cumulative numbers of defined daily doses, throughout the study. Each SU subtype contributed to cumulative dose accretion only when SU were evaluated altogether; otherwise they contributed only to their respective subclass. Cumulative time and dose were used as risk factors for the primary end-point. Direct exposure measurement was not available after December 31, 2008, so last observation was carried forward until the end-point or censor. This was accepted as a tradeoff for some exposure misclassification against reduction in reverse causality.
In vitro and in vivo characterization of fast dissolving tablets containing gliquidone–pluronic solid dispersion
Published in Drug Development and Industrial Pharmacy, 2019
Mohamed S. Mohamed, Wael A. Abdelhafez, Gamal Zayed, Ahmed M. Samy
Gliquidone (GLI) is a second generation sulfonylurea used in the treatment of type 2 diabetes mellitus; it is practically insoluble in water and belongs to class II drugs in the Biopharmaceutical Classification System, which have low and irregular bioavailability after oral administration [1]. Several methods have been employed to improve the solubility and bioavailability of poorly soluble drugs such as salt formation, emulsification, micronization, complexation, and formation of solid solution [2]. Solid dispersion (SD) includes a dispersion of one or more of the active ingredients in an inert hydrophilic carrier in solid state prepared by melting, kneading, or solvent evaporation methods [3]. Solid dispersion can improve dissolution rate of poorly soluble drugs through generation of higher energy metastable forms of the drug based on type and quantity of carrier. In addition to, the presence of carrier may prevent aggregation of fine particles producing a higher surface area of the drug available for dissolution [4]. Many hydrophilic carriers like polyethylene glycols, polyvinylpyrrolidone, mannitol, urea, and poloxamers can be used to increase dissolution rate of hydrophobic drugs [5]. The attempts that have been reported to enhance dissolution rate of GLI are the complexation with β cyclodextrin and hydroxypropyl β cyclodextrin, and the solid dispersion with PVP k30 [6,7]. Poloxamers (PXM) are non-ionic tri-block copolymers composed of a hydrophobic chain of polyoxypropylene and two hydrophilic chains of polyoxyethylene. They are widely used as solubilizing agents, emulsifiers, suspension stabilizers, wetting agents and have been reported for improving the solubility and bioavailability of different hydrophobic drugs in solid dosage forms [8–11]. PXM 188 (pluronic F-68) has been used to improve the dissolution of simvastatine, and dompridone and the obtained solid dispersions have been incorporated in fast dissolving tablets [12,13]. Fast dissolving tablets (FDTs) are solid unit dosage forms which dissolve or disintegrate in the oral cavity upon contact with saliva, resulting in solution or suspension of the administered drug without the need of water [14]. FDTs are advantageous especially for pediatric and elderly patients who have difficulty in swallowing the conventional tablets and capsules [15]. In addition to improvement of the compliance and acceptability of patients, FDTs show enhancement of the dissolution rate and avoidance of first pass metabolism through pregastric absorption, which in turn improve the drug bioavailability [16]. The technologies utilized for the manufacturing of FDTs are freeze drying, molding, sublimation, direct compression, spray drying, and mass extrusion [17]. According to European pharmacopeia, FDTs should disintegrate in less than 3 min [18].