Influence of Vehicle on Gastrointestinal Absorption of Phenytoin in Rats
The relationship between the bioavailability of various phenytoin (DPH) suspensions and the physicochemical properties of the vehicle as well as the physiological factors influencing the bioavailabllity were studied in rats. The vehicles used were aqueous solutions of methylcellulose (0.1, 0.5 and 1...
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| Published in | Chemical & pharmaceutical bulletin Vol. 33; no. 11; pp. 4981 - 4988 |
|---|---|
| Main Authors | , , , , |
| Format | Journal Article |
| Language | English |
| Published |
Tokyo
The Pharmaceutical Society of Japan
01.01.1985
公益社団法人日本薬学会 Maruzen Japan Science and Technology Agency |
| Subjects | |
| Online Access | Get full text |
| ISSN | 0009-2363 1347-5223 |
| DOI | 10.1248/cpb.33.4981 |
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| Abstract | The relationship between the bioavailability of various phenytoin (DPH) suspensions and the physicochemical properties of the vehicle as well as the physiological factors influencing the bioavailabllity were studied in rats. The vehicles used were aqueous solutions of methylcellulose (0.1, 0.5 and 1%), 1% polysorbate 80 aqueous solution, sesame oil and sesame oil emulsion. The gastric emptying time was determined from the amount of phenol red remaining in the stomach after oral administration. As the gastric emptying time increased, the area under the blood concentration-time curve, the maximum blood concentration and the time required to reach the maximum blood concentration increased. The gastric emptying time became smaller as the fluidity of the vehicle increased. Clearly, the viscosity is an important factor affecting the bioavailability of DPH. As the gastric emptying and the dissolution rate slowed down, the apparent absorption rate constant (ka) became small. However, ka obtained from an oily suspension was only one-third of the value obtained from an aqueous suspension. Thus, the mechanism by which DPH is absorbed from the digestive tract after administration as an oily suspension appears to be considerably different from that after administration as an oily suspension appears to be considerably different from that after administration as an aqueous suspension. The value of ka obtained from the in vivo absorption study was about half of that found in situ. These results suggest that ka obtained from the in vivo absorption study includes the transit rate of suspension from the stomach to the intestinal tract. |
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| AbstractList | The relationship between the bioavailability of various phenytoin (DPH) suspensions and the physicochemical properties of the vehicle as well as the physiological factors influencing the bioavailabllity were studied in rats. The vehicles used were aqueous solutions of methylcellulose (0.1, 0.5 and 1%), 1% polysorbate 80 aqueous solution, sesame oil and sesame oil emulsion. The gastric emptying time was determined from the amount of phenol red remaining in the stomach after oral administration. As the gastric emptying time increased, the area under the blood concentration-time curve, the maximum blood concentration and the time required to reach the maximum blood concentration increased. The gastric emptying time became smaller as the fluidity of the vehicle increased. Clearly, the viscosity is an important factor affecting the bioavailability of DPH. As the gastric emptying and the dissolution rate slowed down, the apparent absorption rate constant (ka) became small. However, ka obtained from an oily suspension was only one-third of the value obtained from an aqueous suspension. Thus, the mechanism by which DPH is absorbed from the digestive tract after administration as an oily suspension appears to be considerably different from that after administration as an oily suspension appears to be considerably different from that after administration as an aqueous suspension. The value of ka obtained from the in vivo absorption study was about half of that found in situ. These results suggest that ka obtained from the in vivo absorption study includes the transit rate of suspension from the stomach to the intestinal tract. The relationship between the bioavailability of various phenytoin (DPH) suspensions and the physicochemical properties of the vehicle as well as the physiological factors influencing the bioavailabllity were studied in rats. The vehicles used were aqueous solutions of methylcellulose (0.1,0.5 and 1%), 1% polysorbate 80 aqueous solution, sesame oil and sesame oil emulsion. The gastric emptying time was determined from the amount of phenol red remaining in the stomach after oral administration. As the gastric emptying time increased, the area under the blood concentration-time curve, the maximum blood concentration and the time required to reach the maximum blood concentration increased. The gastric emptying time became smaller as the fluidity of the vehicle increased. Clearly, the viscosity is an important factor affecting the bioavailability of DPH. As the gastric emptying and the dissolution rate slowed down, the apparent absorption rate constant (k_a) became small. However, k_a obtained from an oily suspension was only one-third of the value obtained from an aqueous suspension. Thus, the mechanism by which DPH is absorbed from the digestive tract after administration as an oily suspension appears to be considerably different from that after administration as an oily suspension appears to be considerably different from that after administration as an aqueous suspension. The value of k_a obtained from the in vivo absorption study was about half of that found in situ. These results suggest that k_a obtained from the in vivo absorption study includes the transit rate of suspension from the stomach to the intestinal tract. |
| Author | YATA, NOBORU MIZUNO, NOBUYASU SHINKUMA, DENJI HAMAGUCHI, TSUNEO YAMANAKA, YOU |
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| References | 1) D. E. Wurster and P. W. Taylor, J. Pharm. Sci., 54,169 (1965 P. J. Pentikäinen, P. J. Neuvonen, and S. M. Elfving, Eur. J. Clin. Pharmacol., 9, 213 (1975). 2) J. H. Tyrer, M. J. Eadie, J. M. Sutherland, and W. D. Hooper, Br. Med. J., 4, 271 (1970). Y. Sawayanagi, N. Nambu, and T. Nagai, Chem. Pharm. Bull., 31, 2064 (1983). H. Sekikawa, J. Fujiwara, T. Naganuma, M. Nakano, and T. Arita, Chem. Pharm. Bull., 26, 3033 (1978) 19) J. N. Hunt and J. D. Pathak, J. Physiol. (London), 154, 254 (1960). 14) T. R. Bates and J. A. Sequeira, J. Pharm. Sci., 64, 793 (1975). 17) J. N. Hunt, M. T. Knox, and A. Oginski, J. Physiol. (London), 178, 92 (1965). 13) P. C. Reynell and G. H. Spray, J. Physiol. (London), 131, 452 (1956). 7) S. Chakrabarti and F. M. Belpaire, J. Pharm. Pharmacol., 30, 330 (1978). 23) T. Noguchi, Y. Jinguji, T. Kimura, S. Muranishi, and H. Sezaki, Chem. Pharm. Bull., 23, 782 (1975). D. Shinkuma, H. Hashimoto, Y. Yamanaka, Y. Morita, and N. Mizuno, Yakuzaigaku, 39, 121 (1979) 22) K. Kakemi, H. Sezaki, S. Muranishi, H. Ogata, and S. Isemura, Chem. Pharm. Bull., 20, 708 (1972 4) S. Feldman, H. B. Kostenbauder, and S. Riegelman, J. Am. Pharm. Assoc., NS15, 539 (1975). 9) J. R. Weeks and J. D. Davis, J. Appl. Physiol., 19, 540 (1964 P. J. Neuvonen, P. J. Pentikäinen, and S. M. Elfving, Int. J. Clin. Pharmacol., 15, 84 (1977) 8) D. Shinkuma, T. Hamaguchi, C. Muro, F. Oota, Y. Yamanaka, and N. Mizuno, Int. J. Pharmaceut., 9, 17 (1981). 18) G. Levy and W. J. Jusko, J. Pharm. Sci., 54, 219 (1965). R. A. Upton, J. Pharm. Sci., 64, 112 (1975). 21) V. Manninen, A. Apajalahti, J. Melin, and M. Karesoja, Lancet, i, 398 (1973). P. Kabasakalian, M. Katz, B. Rosenkrantz, and E. Townley, J. Pharm. Sci., 59, 595 (1970). 15) P. J. Carrigan and T. R. Bates, J. Pharm. Sci., 62, 1476 (1973). A. J. Aguiar, J. Krc, Jr., A. W. Kinkel, and J. C. Samyn, J. Pharm. Sci., 56, 847 (1967). 5) D. Shinkuma, H. Hashimoto, Y. Yamanaka, and Y. Morita, Acta Med. Hyogo, 1, 141 (1976). 11) Y. Utsui, T. Maeda, K. Tan, and M. Hashimoto, The 98th Annual Meeting of the Pharmaceutical Society of Japan, Okayama, April 1978. K. Kakemi, H. Sezaki, S. Muranishi, H. Ogata, and K. Giga, Chem. Pharm. Bull., 20, 715 (1972) 20) R. G. Crounse, J. Invest. Dermatol., 37, 529 (1961 6) K. Yamamoto, M. Nakano, T. Arita, Y. Takayama, and Y. Nakai, J. Pharm. Sci., 65, 1484 (1976 16) J. N. Hunt and I. MacDonald, J. Physiol. (London), 126, 459 (1954). H. Ogata, K. Kakemi, S. Muranishi, and H. Sezaki, Chem. Pharm. Bull., 23, 707 (1975). 3) L. Lund, Eur. J. Clin. Pharmacol., 7, 119 (1974 10) J. J. Ashley and G. Levy, Res. Commun. Chem. Pathol. Pharmacol., 4, 297 (1972). 24) T. Noguchi, C. Takahashi, T. Kimura, S. Muranishi, and H. Sezaki, Chem. Pharm. Bull., 23, 775 (1975). M. Gibaldi and D. Perrier, "Pharmacokinetics," 2nd ed., Marcel Dekker, Inc., New York, 1982, pp. 145-198. 12) K. Yamaoka and Y. Tanigawara, "Yakubutsusokudoronnyumon," Nankodo, Ltd., Tokyo, 1983, pp. 91-105 |
| References_xml | – reference: 1) D. E. Wurster and P. W. Taylor, J. Pharm. Sci., 54,169 (1965); – reference: 5) D. Shinkuma, H. Hashimoto, Y. Yamanaka, and Y. Morita, Acta Med. Hyogo, 1, 141 (1976). – reference: 13) P. C. Reynell and G. H. Spray, J. Physiol. (London), 131, 452 (1956). – reference: 24) T. Noguchi, C. Takahashi, T. Kimura, S. Muranishi, and H. Sezaki, Chem. Pharm. Bull., 23, 775 (1975). – reference: P. Kabasakalian, M. Katz, B. Rosenkrantz, and E. Townley, J. Pharm. Sci., 59, 595 (1970). – reference: 8) D. Shinkuma, T. Hamaguchi, C. Muro, F. Oota, Y. Yamanaka, and N. Mizuno, Int. J. Pharmaceut., 9, 17 (1981). – reference: 22) K. Kakemi, H. Sezaki, S. Muranishi, H. Ogata, and S. Isemura, Chem. Pharm. Bull., 20, 708 (1972); – reference: 21) V. Manninen, A. Apajalahti, J. Melin, and M. Karesoja, Lancet, i, 398 (1973). – reference: K. Kakemi, H. Sezaki, S. Muranishi, H. Ogata, and K. Giga, Chem. Pharm. Bull., 20, 715 (1972); – reference: 17) J. N. Hunt, M. T. Knox, and A. Oginski, J. Physiol. (London), 178, 92 (1965). – reference: M. Gibaldi and D. Perrier, "Pharmacokinetics," 2nd ed., Marcel Dekker, Inc., New York, 1982, pp. 145-198. – reference: 15) P. J. Carrigan and T. R. Bates, J. Pharm. Sci., 62, 1476 (1973). – reference: Y. Sawayanagi, N. Nambu, and T. Nagai, Chem. Pharm. Bull., 31, 2064 (1983). – reference: 10) J. J. Ashley and G. Levy, Res. Commun. Chem. Pathol. Pharmacol., 4, 297 (1972). – reference: 6) K. Yamamoto, M. Nakano, T. Arita, Y. Takayama, and Y. Nakai, J. Pharm. Sci., 65, 1484 (1976); – reference: R. A. Upton, J. Pharm. Sci., 64, 112 (1975). – reference: P. J. Pentikäinen, P. J. Neuvonen, and S. M. Elfving, Eur. J. Clin. Pharmacol., 9, 213 (1975). – reference: 7) S. Chakrabarti and F. M. Belpaire, J. Pharm. Pharmacol., 30, 330 (1978). – reference: P. J. Neuvonen, P. J. Pentikäinen, and S. M. Elfving, Int. J. Clin. Pharmacol., 15, 84 (1977); – reference: 11) Y. Utsui, T. Maeda, K. Tan, and M. Hashimoto, The 98th Annual Meeting of the Pharmaceutical Society of Japan, Okayama, April 1978. – reference: 16) J. N. Hunt and I. MacDonald, J. Physiol. (London), 126, 459 (1954). – reference: 12) K. Yamaoka and Y. Tanigawara, "Yakubutsusokudoronnyumon," Nankodo, Ltd., Tokyo, 1983, pp. 91-105; – reference: D. Shinkuma, H. Hashimoto, Y. Yamanaka, Y. Morita, and N. Mizuno, Yakuzaigaku, 39, 121 (1979); – reference: 20) R. G. Crounse, J. Invest. Dermatol., 37, 529 (1961); – reference: 2) J. H. Tyrer, M. J. Eadie, J. M. Sutherland, and W. D. Hooper, Br. Med. J., 4, 271 (1970). – reference: 18) G. Levy and W. J. Jusko, J. Pharm. Sci., 54, 219 (1965). – reference: 14) T. R. Bates and J. A. Sequeira, J. Pharm. Sci., 64, 793 (1975). – reference: H. Ogata, K. Kakemi, S. Muranishi, and H. Sezaki, Chem. Pharm. Bull., 23, 707 (1975). – reference: 4) S. Feldman, H. B. Kostenbauder, and S. Riegelman, J. Am. Pharm. Assoc., NS15, 539 (1975). – reference: H. Sekikawa, J. Fujiwara, T. Naganuma, M. Nakano, and T. Arita, Chem. Pharm. Bull., 26, 3033 (1978); – reference: 19) J. N. Hunt and J. D. Pathak, J. Physiol. (London), 154, 254 (1960). – reference: 23) T. Noguchi, Y. Jinguji, T. Kimura, S. Muranishi, and H. Sezaki, Chem. Pharm. Bull., 23, 782 (1975). – reference: 3) L. Lund, Eur. J. Clin. Pharmacol., 7, 119 (1974); – reference: A. J. Aguiar, J. Krc, Jr., A. W. Kinkel, and J. C. Samyn, J. Pharm. Sci., 56, 847 (1967). – reference: 9) J. R. Weeks and J. D. Davis, J. Appl. Physiol., 19, 540 (1964); |
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| SubjectTerms | Animals Anticonvulsants. Antiepileptics. Antiparkinson agents aqueous suspension bioavailability Biological and medical sciences Biological Availability dissolution rate Intestinal Absorption Male Medical sciences Neuropharmacology oily suspension Pharmaceutical Vehicles Pharmacology. Drug treatments phenytoin Phenytoin - blood Phenytoin - metabolism phenytoin solubility rat Rats Rats, Inbred Strains vehicle viscosity |
| Title | Influence of Vehicle on Gastrointestinal Absorption of Phenytoin in Rats |
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