Shikimic acid (SA), extracted from the fruit of shikimi-no-ki, is used both as a preservative in the food industry and as an intermediate for a variety of active ingredients with a wide range of pharmacological functions. A deeper understanding of the pharmacokinetic process of SA in pigs and its impact on humoral immunity could prove invaluable in facilitating its clinical application in veterinary and human medicine. The pharmacokinetic study employed a two-period, two-sequence, crossover design to animal experiments and developed a novel method of pig plasma preparation using water as an extractant and ionization promoter, followed by purification and enrichment on a MAX solid phase extraction (SPE) column. The results showed that SA is rapidly absorbed after intragastric administration (50 mg/kg BW), reaching a plasma C_max of 10,823.44 ng/mL at 1.78 h, followed by rapid elimination, with a t_1/2 of 1.81 h, consistent with a one-compartment model. The results for intravenous administration (2 mg/kg BW) were consistent with a two-compartment open model with a t_1/2 of 3.66 h, with concentrations below the limit of quantification (LOQ) observed beyond 12 h postdose. The absolute bioavailability of SA in pigs was calculated to be 21.68%. Furthermore, the Pearson’s correlation analysis demonstrated a strong positive correlation between SA concentration in pig plasma and the changes of C3, C4 and IgG, IgA, and IgM (0.6 < R < 1, P < 0.0001). A more detailed pharmacokinetic–pharmacodynamic (PK–PD) modeling analysis of the intravenous group revealed the EC₅₀/C_max values of approximately 10%, with all γ values exceeding 3. This study was the inaugural investigation into the pharmacokinetics of SA in growing pigs, and it also revealed that SA has the potential to act as an immunopotentiator.

中文翻译：

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药代动力学 - 莽草酸对生长猪免疫增强作用的药效学建模


莽草酸 （SA） 是从莽香味之气的果实中提取的，在食品工业中既用作防腐剂，也用作具有广泛药理功能的各种活性成分的中间体。更深入地了解 SA 在猪体内的药代动力学过程及其对体液免疫的影响，对于促进其在兽医和人类医学中的临床应用可能具有不可估量的价值。药代动力学研究采用双周期、双序列、动物实验交叉设计，开发了一种使用水作为萃取剂和电离促进剂制备猪血浆的新方法，然后在 MAX 固相萃取 （SPE） 柱上进行纯化和富集。结果显示，SA 在胃内给药 （50 mg/kg BW） 后被迅速吸收，在 1.78 小时达到血浆 C_max 为 10,823.44 ng/mL，然后快速消除，t_1/2 为 1.81 h，与单室模型一致。静脉内给药 （2 mg/kg BW） 的结果与双室开放模型一致，t_1/2 为 3.66 h，给药后 12 小时后观察到浓度低于定量限 （LOQ）。计算出 SA 在猪体内的绝对生物利用度为 21.68%。此外，Pearson 相关性分析表明，猪血浆中 SA 浓度与 C3 、 C4 和 IgG 、 IgA 和 IgM 的变化呈强正相关 （0.6 < R < 1， P < 0.0001）。静脉注射组更详细的药代动力学-药效学 （PK-PD） 模型分析显示，EC₅₀/C_max 值约为 10%，所有 γ 值均超过 3。 这项研究是对 SA 在生长猪中的药代动力学的首次研究，它还揭示了 SA 具有作为免疫增强剂的潜力。