Wanner M, Küng K, Riond J L
Institute of Veterinary Physiology, University of Zürich, Switzerland.
Zentralbl Veterinarmed A. 1996 Oct;43(8):473-81. doi: 10.1111/j.1439-0442.1996.tb00477.x.
The bioavailability of two different forms of medicated feed containing 2000 mg sulfadimidine (SDM) per kg was determined in three groups of eight piglets. In the first group, pharmacokinetic parameters of SDM were determined after a single intravenous dose of 10 mg/kg body weight and after single oral doses of 45 mg/kg body weight ingested either as an oleus solution sprayed directly onto the feed pellets ready for use (SPR) or as a commercially available premix incorporated into the feed before pelletising (PMX). After the single intravenous administration, the mean +/- SD of the volume of distribution was 0.34 +/- 0.05 l/kg, the total body clearance 0.37 +/- 0.07 ml/min.kg, the mean residence time 15.5 +/- 2.5 h, and the elimination half-life 11.1 +/- 2.0 h. Although no statistical significance existed, a single meal with PMX was associated with slightly higher mean values for the maximum serum concentration (Cmax), the time to reach Cmax, and the bioavailability (52.98 +/- 6.60 micrograms/ml, 6.8 +/- 1.1 h, 59.7 +/- 12.1%, respectively, vs. 40.04 +/- 13.19 micrograms/ml, 6.0 +/- 1.4 h, 49.0 +/- 18.6 for SPR). The remaining two groups of piglets received medicated feed with either SPR or PMX during a 3-day period both with restrictive (twice-daily) or ad libitum feeding according to a cross-over design. In all four cases, potentially efficacious plasma SDM concentrations between 50 and 150 micrograms/ml were obtained within 24 h after initiation of the treatment. With PMX, plasma concentrations tended to be higher than with SPR with both feeding regimens. Ad libitum feeding was associated with a significantly higher food intake and hence a higher SDM intake resulting in higher plasma concentrations. Additionally, plasma concentrations were more constant over time with ad libitum feeding whereas they declined considerably between meals in restrictively fed animals. In vitro dissolution tests of the two types of medicated feed revealed that SDM was rapidly released from SPR (58% within 15 min) and that SDM release from PMX was markedly slower (3% within 15 min). Despite the relatively slow rate of in vitro dissolution, in vivo absorption of SDM was satisfactory. It is concluded that both forms of SDM medicated feed may be considered bioequivalent and potentially efficacious in piglets.
在三组每组八头仔猪中测定了两种不同形式的含药饲料（每千克含2000毫克磺胺二甲嘧啶（SDM））的生物利用度。在第一组中，测定了静脉注射单剂量10毫克/千克体重以及口服单剂量45毫克/千克体重后的SDM药代动力学参数，口服的45毫克/千克体重剂量的SDM分别以直接喷洒在即用型饲料颗粒上的油溶液（SPR）形式或制粒前混入饲料中的市售预混剂（PMX）形式摄入。单次静脉给药后，分布容积的均值±标准差为0.34±0.05升/千克，全身清除率为0.37±0.07毫升/分钟·千克，平均驻留时间为15.5±2.5小时，消除半衰期为11.1±2.0小时。尽管无统计学显著性差异，但单次给予PMX后，最大血清浓度（Cmax）、达到Cmax的时间和生物利用度的均值略高（分别为52.98±6.60微克/毫升、6.8±1.1小时、59.7±12.1%，而SPR分别为40.04±13.19微克/毫升、6.0±1.4小时、49.0±18.6%）。其余两组仔猪按照交叉设计在3天期间分别接受含SPR或PMX的含药饲料，采用限制饲喂（每日两次）或自由采食。在所有四种情况下，治疗开始后24小时内血浆SDM浓度均达到50至150微克/毫升的潜在有效浓度。采用PMX时，两种饲喂方案下的血浆浓度均倾向于高于采用SPR时。自由采食与显著更高的采食量相关，因此SDM摄入量更高，导致血浆浓度更高。此外，自由采食时血浆浓度随时间更稳定，而限制饲喂的动物在两餐之间血浆浓度大幅下降。两种类型含药饲料的体外溶出试验表明，SDM从SPR中快速释放（15分钟内释放58%），而从PMX中的释放明显较慢（15分钟内释放3%）。尽管体外溶出速率相对较慢，但SDM的体内吸收情况良好。结论是两种形式的SDM含药饲料在仔猪中均可视为生物等效且可能有效。
