The Experts below are selected from a list of 255 Experts worldwide ranked by ideXlab platform
Gordon L Amidon - One of the best experts on this subject based on the ideXlab platform.
-
segmental dependent membrane permeability along the intestine following Oral Drug Administration evaluation of a triple single pass intestinal perfusion tspip approach in the rat
European Journal of Pharmaceutical Sciences, 2009Co-Authors: Arik Dahan, Brady T West, Gordon L AmidonAbstract:Abstract In this paper we evaluate a modified approach to the traditional single-pass intestinal perfusion (SPIP) rat model in investigating segmental-dependent permeability along the intestine following Oral Drug Administration. Whereas in the traditional model one single segment of the intestine is perfused, we have simultaneously perfused three individual segments of each rat intestine: proximal jejunum, mid-small intestine and distal ileum, enabling to obtain tripled data from each rat compared to the traditional model. Three Drugs, with different permeabilities, were utilized to evaluate the model: metoprolol, propranolol and cimetidine. Data was evaluated in comparison to the traditional method. Metoprolol and propranolol showed similar Peff values in the modified model in all segments. Segmental-dependent permeability was obtained for cimetidine, with lower Peff in the distal parts. Similar Peff values for all Drugs were obtained in the traditional method, illustrating that the modified model is as accurate as the traditional, throughout a wide range of permeability characteristics, whether the permeability is constant or segment-dependent along the intestine. Three-fold higher statistical power to detect segmental-dependency was obtained in the modified approach, as each subject serves as his own control. In conclusion, the Triple SPIP model can reduce the number of animals utilized in segmental-dependent permeability research without compromising the quality of the data obtained.
Arik Dahan - One of the best experts on this subject based on the ideXlab platform.
-
segmental dependent permeability throughout the small intestine following Oral Drug Administration single pass vs doluisio approach to in situ rat perfusion
International Journal of Pharmaceutics, 2016Co-Authors: Isabel Lozoyaagullo, Avital Beig, Noa Fine, Yael Cohen, Marta Gonzalezalvarez, Matilde Merinosanjuan, Isabel Gonzalezalvarez, Marival Bermejo, Arik DahanAbstract:Abstract Intestinal Drug permeability is position dependent and pertains to a specific point along the intestinal membrane, and the resulted segmental-dependent permeability phenomenon has been recognized as a critical factor in the overall absorption of Drug following Oral Administration. The aim of this research was to compare segmental-dependent permeability data obtained from two different rat intestinal perfusion approaches: the single-pass intestinal perfusion (SPIP) model and the closed-loop (Doluisio) rat perfusion method. The rat intestinal permeability of 12 model Drugs with different permeability characteristics (low, moderate, and high, as well as passively and actively absorbed) was assessed in three small intestinal regions: the upper jejunum, mid-small intestine, and the terminal ileum, using both the SPIP and the Doluisio experimental methods. Excellent correlation was evident between the two approaches, especially in the upper jejunum ( R 2 = 0.95). Significant regional-dependent permeability was found in half of Drugs studied, illustrating the importance and relevance of segmental-dependent intestinal permeability. Despite the differences between the two methods, highly comparable results were obtained by both methods, especially in the medium-high P eff range. In conclusion, the SPIP and the Doluisio method are both equally useful in obtaining crucial segmental-dependent intestinal permeability data.
-
segmental dependent membrane permeability along the intestine following Oral Drug Administration evaluation of a triple single pass intestinal perfusion tspip approach in the rat
European Journal of Pharmaceutical Sciences, 2009Co-Authors: Arik Dahan, Brady T West, Gordon L AmidonAbstract:Abstract In this paper we evaluate a modified approach to the traditional single-pass intestinal perfusion (SPIP) rat model in investigating segmental-dependent permeability along the intestine following Oral Drug Administration. Whereas in the traditional model one single segment of the intestine is perfused, we have simultaneously perfused three individual segments of each rat intestine: proximal jejunum, mid-small intestine and distal ileum, enabling to obtain tripled data from each rat compared to the traditional model. Three Drugs, with different permeabilities, were utilized to evaluate the model: metoprolol, propranolol and cimetidine. Data was evaluated in comparison to the traditional method. Metoprolol and propranolol showed similar Peff values in the modified model in all segments. Segmental-dependent permeability was obtained for cimetidine, with lower Peff in the distal parts. Similar Peff values for all Drugs were obtained in the traditional method, illustrating that the modified model is as accurate as the traditional, throughout a wide range of permeability characteristics, whether the permeability is constant or segment-dependent along the intestine. Three-fold higher statistical power to detect segmental-dependency was obtained in the modified approach, as each subject serves as his own control. In conclusion, the Triple SPIP model can reduce the number of animals utilized in segmental-dependent permeability research without compromising the quality of the data obtained.
Chung-gyu Park - One of the best experts on this subject based on the ideXlab platform.
-
Gastrostomy tube placement for long-term Oral Drug Administration in non-human primates.
Xenotransplantation, 2017Co-Authors: Jun Seop Shin, Il Hee Yoon, Won Young Jeong, Chung-gyu ParkAbstract:Background Non-human primates (NHPs) are often used as recipients in preclinical transplantation research that in most cases involves Administration of various Drugs including immunosuppressants. Long-term Oral Drug Administration, particularly tacrolimus, is challenging in the transplant recipient NHPs. Oral Drug Administration method using the mixture of Drug and fruit juice has been used in NHPs, but this is not always effective in all monkeys. To those monkeys who are poorly compliant, Oral Drug Administration in restraint or Administration using gastrostomy tube should be necessary. The aim of this study was to compare the efficacy of between Oral Drug Administration in restraint and Administration using gastrostomy tube and to report complications and solutions to overcome the problems related to gastrostomy tube for long-term Oral Drug dosing in rhesus monkeys. Methods Fifteen of 4- to 5-year-old male and female healthy rhesus monkeys weighing 5.0-6.8 kg were used as recipients for porcine pancreatic islet transplantation. Oral Drug Administration in restraint was used for four monkeys, and gastrostomy tube was placed to other 11 monkeys (8-French Feeding tube, n=6; Tri-Funnel Replacement Gastrostomy tube, n=5). Oral immunosuppressive Drugs such as sirolimus and tacrolimus were administered through the tube. The efficacy and the extent of ease for Administration and related complications were compared between two groups. Results and Conclusions The complication of gastrostomy included a transient inflammation in the skin and peritonitis caused by a leakage around implantation site (one case), which could be overcome by changing suture method and tube type to interlocking box suture and Tri-Funnel Replacement Gastrostomy tube, respectively. Despite these complications, Oral Drug Administration using gastrostomy tube allowed us to perform accurate dosage of Drug Administration and to reduce the stress that both the monkey and the researcher may experience. Taken together, this study showed that gastrostomy tube placement is a better alternative to Oral Drug Administration in restraint for long-term Oral Drug Administration in rhesus monkeys who tend to refuse to eat the mixture of Drug and fruit juice.
Brady T West - One of the best experts on this subject based on the ideXlab platform.
-
segmental dependent membrane permeability along the intestine following Oral Drug Administration evaluation of a triple single pass intestinal perfusion tspip approach in the rat
European Journal of Pharmaceutical Sciences, 2009Co-Authors: Arik Dahan, Brady T West, Gordon L AmidonAbstract:Abstract In this paper we evaluate a modified approach to the traditional single-pass intestinal perfusion (SPIP) rat model in investigating segmental-dependent permeability along the intestine following Oral Drug Administration. Whereas in the traditional model one single segment of the intestine is perfused, we have simultaneously perfused three individual segments of each rat intestine: proximal jejunum, mid-small intestine and distal ileum, enabling to obtain tripled data from each rat compared to the traditional model. Three Drugs, with different permeabilities, were utilized to evaluate the model: metoprolol, propranolol and cimetidine. Data was evaluated in comparison to the traditional method. Metoprolol and propranolol showed similar Peff values in the modified model in all segments. Segmental-dependent permeability was obtained for cimetidine, with lower Peff in the distal parts. Similar Peff values for all Drugs were obtained in the traditional method, illustrating that the modified model is as accurate as the traditional, throughout a wide range of permeability characteristics, whether the permeability is constant or segment-dependent along the intestine. Three-fold higher statistical power to detect segmental-dependency was obtained in the modified approach, as each subject serves as his own control. In conclusion, the Triple SPIP model can reduce the number of animals utilized in segmental-dependent permeability research without compromising the quality of the data obtained.
Jennifer B Dressman - One of the best experts on this subject based on the ideXlab platform.
-
whole body physiologically based pharmacokinetic population modelling of Oral Drug Administration inter individual variability of cimetidine absorption
Journal of Pharmacy and Pharmacology, 2009Co-Authors: Stefan Willmann, Andrea N Edginton, Marcus Kleinebesten, Ekarat Jantratid, Kirstin Thelen, Jennifer B DressmanAbstract:Objectives Inter-individual variability of gastrointestinal physiology and transit properties can greatly influence the pharmacokinetics of an Orally administered Drug in vivo. To predict the expected range of pharmacokinetic plasma concentrations after Oral Drug Administration, a physiologically based pharmacokinetic population model for gastrointestinal transit and absorption was developed and evaluated. Methods Mean values and variability measures of model parameters affecting the rate and extent of cimetidine absorption, such as gastric emptying, intestinal transit times and effective surface area of the small intestine, were obtained from the literature. Various scenarios incorporating different extents of inter-individual physiological variability were simulated and the simulation results were compared with experimental human study data obtained after Oral cimetidine Administration of four different tablets with varying release kinetics. Key findings The inter-individual variability in effective surface area was the largest contributor to absorption variability. Based on in-vitro dissolution profiles, the mean plasma cimetidine concentration–time profiles as well as the inter-individual variability could be well described for three cimetidine formulations. In the case of the formulation with the slowest dissolution kinetic, model predictions on the basis of the in-vitro dissolution profile underestimated the plasma exposure. Conclusions The model facilitates predictions of the inter-individual pharmacokinetic variability after Oral Drug Administration for immediate and extended-release formulations of cimetidine, given reasonable in-vitro dissolution kinetics.