Oral pharmacokinetics of the acidic drugs, diclofenac and sulfamonomethoxine in male Shiba goats

Abstract

In the present study, we examined the oral pharmacokinetics of the acidic drugs, diclofenac (DF) and sulfamonomethoxine (SMM), which have different physicochemical properties, in Shiba goats. DF and SMM were intravenously and orally administered to 5 male goats using a crossover design. The Tmax of DF and SMM were reached 1.5 and 5.6 hr after they have been orally administered, respectively, and this was followed by their slow elimination. The elimination of both drugs was markedly faster after being intravenously rather than orally administered, which indicated flip-flop phenomena after the oral administration. The mean absorption times (MATs) of DF and SMM were 6 and 15 hr, respectively. This slow absorption may have been due to slow gastric emptying in goats. The large difference observed in MATs between DF and SMM may have been because DF, which is more lipophilic than SMM, was partly absorbed from the forestomach. Therefore, these results suggest that the absorption of highly lipophilic drugs from the forestomach may be markedly high in Shiba goats. In case of drugs whose elimination is quite fast, their efficacies may appear from the early stage after oral administration even in ruminants, because elimination rate is the determinant factor of Tmax in flip-flop phenomena. Such drugs may be used orally even in ruminants.

Oral pharmacokinetics of acetaminophen to evaluate gastric emptying profiles of Shiba goats

“…). These values are similar to those of DF (6.75 ± 2.74 and 4.13 ± 1.94 hr, respectively) in a previous study using Shiba goats [ 4 ]. These results suggested that AAP was absorbed more from the forestomach, similar to DF.…”

“…Although the oral route is considered to be inappropriate for ruminants, we previously demonstrated the effectiveness of this route for diclofenac (DF) and sulphamonomethoxine (SMM) in Shiba goats [ 4 ]; the mean absorption time (MAT) of DF (6.05 hr) was less than half that of SMM (15.1 hr). These findings suggested that the short MAT of DF was due to its marked absorption from the forestomach while the long MAT of SMM was due to a long gastric emptying time; however, gastric emptying time needs to be estimated in order to confirm this.…”

“…The stability of AAP in the rumen juice was determined as described previously [ 4 ]. Briefly, 40 m l of rumen fluid was collected from two goats using a catheter, pooled and processed for incubation immediately after its collection.…”

Rapid absorption of diclofenac and acetaminophen after their oral administration to cattle

“…This large volume may result in slow gastric emptying and thus the markedly slower absorption of drugs after their oral administration than that in monogastric animal species. Elbadawy et al [ 7 ] reported that the mean absorption time (MAT) of sulphamonomethoxine was very long (approximately 15 hr) following its oral administration to Shiba goats, which are relatively small ruminants, and concluded that this long MAT may be the result of slow gastric emptying.…”

“…Elbadawy et al . [ 7 ] found that, after it oral administration to Shiba goats, the absorption of diclofenac (DF; MAT of approximately 6 hr) was markedly faster than that of sulphamonomethoxine (MAT of approximately 15 hr). This finding suggests that DF is rapidly absorbed from the forestomach.…”