Pharmacokinetics of cyclizine following intravenous administration to human volunteers
- Authors: Kanfer, Isadore , Walker, Roderick B
- Date: 1996
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/184389 , vital:44214 , xlink:href="https://doi.org/10.1016/0928-0987(96)00177-7"
- Description: The pharmacokinetics of cyclizine, a piperazine derivative useful in the prevention and treatment of nausea and vomiting, was investigated in six healthy male volunteers following an intravenous bolus dose. The drug is extensively distributed with a mean volume of distribution of 16.50 ± 3.33 l/kg and a mean total clearance of 0.870 ± 0.105 l/h per kg. Urinary excretion data showed that less than one percent of the dose was excreted up to 36 h as unchanged drug in the urine. The extremely low mean renal clearance (0.005 ± 0.002 l/h per kg) for the parent drug comprised only a small proportion of total clearance indicating that urinary excretion of parent drug is not a major route of elimination for cyclizine. The drug appears to exhibit biexponential pharmacokinetics and has a terminal elimination half-life of approximately 13 h.
- Full Text:
- Date Issued: 1996
Bioequivalence assessment of generic products an innovative South African approach
- Authors: Walker, Roderick B , Kanfer, Isadore , Skinner, Michael F
- Date: 2006
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/184256 , vital:44194 , xlink:href="https://doi.org/10.1080/10601330500534014"
- Description: Concurrent with the implementation of new legislation mandating Generic Substitution in South Africa, a new set of guidelines for bioavailability and bioequivalence have been published. Since one of the main objectives of the new legislation in South Africa relating to Generic Substitution is to ensure that medicines of high quality, safety, and efficacy are made more accessible and more affordable to the wider public, the need to speed up approval of such multi-source products has become a regulatory priority. In order to facilitate this process, various bioequivalence issues have been addressed including important issues such as the acceptance criteria and associated bioequivalence intervals, use of a foreign reference product and the issue of assessing highly variable drugs (HVDs). In addition, dispensations have been made with respect to food effect assessment and variability relating to genetic polymorphism in drug metabolism (genotyping/phenotyping). Furthermore, the use of “old” biostudies submitted in support of an application is subject to expiry date. Acceptance of appropriate data requires that specific criteria such as Cmax and AUC, in addition to the usual considerations, also meet the limits specified by the particular registration authority of the country where such products are intended to be marketed. Generally, these limits require that the 90% confidence interval (CI) for AUC and Cmax test/reference ratios lies within the acceptance interval of 0.80–1.25 calculated using log-transformed data. While such acceptance criteria are, in general, ubiquitous, some differences in acceptance criteria do exist between various countries. The new guidelines for bioavailability/bioequivalence studies developed by the South African regulatory authority, the Medicines Control Council (MCC), makes provision for highly variable drugs and the use of a non-South African reference product. The MCC requires that the acceptance criterion for Cmax ratios be set at 0.75–1.33 while maintaining AUC ratios at 0.80–1.25 using a 90% CI. Furthermore, provision is made to apply scaling based on average bioequivalence assessment and, as an interim measure, consideration has also been given to the use of a foreign reference product provided that equivalence between that product and the innovator product currently available on the South African market can be shown using in vitro testing.
- Full Text:
- Date Issued: 2006
In Vitro Release Testing (IVRT) of Topical Hydrocortisone Acetate Creams: a novel approach using positive and negative controls
- Authors: Mudyahoto, Nyengeterai Amanda , Rath, Seeprarani , Ramanah, Ashmita , Kanfer, Isadore
- Date: 2020
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/149849 , vital:38888 , dx.doi.org/10.14227/DT270120P6
- Description: The objective was to develop and validate an in vitro release testing (IVRT) method to assess the release of hydrocortisone acetate (HCA) from five topical formulations. A marketed generic cream containing 1% HCA was used as the reference product. Vertical diffusion cells (VDCs) were used to assess and compare the release rates of HCA from cream formulations containing 0.5%, 1%, and 1.5% HCA. The study describes a novel approach to test the discriminatory power by including both positive and negative controls to declare pharmaceutical equivalence or inequivalence. The validated method was found to be sensitive, linear, precise, reproducible, robust, and selective for the analysis of HCA from topical cream products. Equivalence or inequivalence was established based on SUPAC-SS acceptance criteria using a 90% CI with limits of 75–133.33%. The IVRT method was shown to have discriminatory ability to appropriately measure significant differences in drug release from various cream formulations. This approach also provides useful information for the future development of acceptable IVRT methods to assess topical dosage forms for local action containing different drugs.
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- Date Issued: 2020