Pharmacokinetics of Oral Sulfa Drugs and Gastric Emptying in the Pig

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The plasma pharmacokinetics of sulfamonomethoxine (SMM) and sulfamethazine (SMZ) in the pig were examined after the oral and intravenous (i.v.) administration of the sodium salt solutions. Eight pigs from a commercial breed and 8 Goettingen minipigs were used. Both the C_<max> and t_<max> of SMM and SMZ ranged widely. A flipflop phenomenon was found after the SMM solution but not after the oral SMZ. Duodenal cannulae were inserted in 5 pigs. The SMM solution and the SMM suspension were directly injected into the duodenum through the duodenal cannula. Both C_<max> values were in a narrow range. Both t_<max> values were in a narrow range and were reached within 30 min. There was no flipflop phenomenon. Gastric emptying in the pig was examined using duodenal cannulated pigs. Phenol red solution and SMM suspension were administered orally. The time courses of gastric emptying of the two markers were nearly coincident and they approximated an exponential decrease. The times required for the 50% passage of the marker from the stomach ranged widely between 0.06-7.7h, which may cause the variation in the C_<max> and t_<max> of the sulfadrugs after oral administration. The k-GE (rate constant of the terminal phase of gastric emptying) also ranged widely. Nine k-GE values among 22 were smaller than the minimum value of the SMM k_<el> values, which may cause the flipflop phenomenon of the oral SMM. In contrast, all of the k_<el> values of SMZ were smaller than the minimum value of k-GE. And no flipflop phenomenon was found after the oral SMZ. Accordingly, the pharmacokinetics after the oral sulfonamides solution may be intimately influenced by the gastric emptying.
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Pharmacokinetics of Oral Sulfa Drugs and Gastric Emptying in the Pig

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