豬模式血鉛動力學之研究

Pharmacokinetic Study of Lead Ingestion in Swine

王耀宏(Yao-Horng Wang) ； 吳錦景(Chin-Ching Wu) ； 賴珊湖(San-Hu Lai) ； 陳建志(Chien-Chih Chen) ； 劉正雄(Cheng-Hsiung Liu)

《中華職業醫學雜誌》 13卷4期 (2006/10) Pp. 253-263

摘要

The objectives of this study were to determine the lead concentrations in blood, urine and tissue after a single oral administration of lead to establish the pharmacokinetic characteristics of lead ingestion in swine. Nine hybrid pigs, weighing 30-50 kg, were divided randomly into three groups. Animals in group A and B were orally dosed with 50.0 and 25.0 mg, respectively, of elemental lead per kilogram of body weight (mg/kg BW of lead) using Pb(NO3)2 dissolved in distilled water. Group C was without Pb(NO3)2 as control. The ICP-Mass was used to determine the concentration of lead in blood, urine and tissues. The pharmacokinetic parameters were calculated by using WinNolin software. The unpaired-t test was used for statistical comparison. The T(subscript max) and t(subscript 1/2) in blood were 4.0±2.1 hr and 62.9±8.1 hr for group A, and 12.0±0.0 hr and 619.2±224.0 hr for group B, respectively. The C(subscript max) and AUC in blood were 958.0±97.2 μg/L and 34013.5±2602.9 μg•hr/L for group A, and 376.7±7.4 μg/L and 21257.3±1529.4 μg•hr/L for group B, respectively. These results indicated that the group A produced shorter in the T(subscript max) and t(subscript 1/2), and greater in the C(subscript max) and AUC seems to infer that the lead absorption (ie. accumulated in blood) and clearance from blood was quicker than that of group B significantly (P＜0.05). The T(subscript max) and t(subscript 1/2) in urine were 2.2±0.7 hr and 48.4±11.4 hr for group A, and 6.8±3.2 hr and 30.5±3.7 hr for group B, respectively. The maximum of elimination rate and AURC in urine were 67.68±5.14 μg/hr and 1610.56±195.80 μg•hr/L for group A, and 29.31±6.80 μg/hr and 523.75±94.55 μg•hr/L for group B, respectively. The volume of urine was 4480.4±342.6 mL for group A, and 2375.0±750.8 mL for group B, respectively. These results indicated that the group A in urine produced shorter in the T(subscript max), and higher in the max of elimination rate, AURC, and t(subscript 1/2) seems indicated that the excretion (ie. eliminated via urine) was faster than that of group B significantly (P＜0.05). There were no significant differences in complete blood count and urine routine analysis among the three groups. Also there were no significant differences in tissue lead concentration analyzed between group A and B, nonetheless there were significant differences between control group and lead ingested groups (P＜0.05). The highest lead concentration among those tissues was in the rib (24.093±3.478 μg/g for group A and 20.495±1.679 μg/g for group B); followed by descending order, the liver, hair, femur, kidney, spleen, muscle, heart, lung and brain of two lead-ingested groups but not in the control. In conclusion, this study demonstrated that a single oral administration of lead element produced a complex pharmacokinetics resemble to the orally repeated consumption of lead in swine. The possibility of the blood-compartment and the complex pharmacokinetics were discussed.

關鍵字

藥物動力學 ； 硝酸鉛 ； 豬

並列摘要

The objectives of this study were to determine the lead concentrations in blood, urine and tissue after a single oral administration of lead to establish the pharmacokinetic characteristics of lead ingestion in swine. Nine hybrid pigs, weighing 30-50 kg, were divided randomly into three groups. Animals in group A and B were orally dosed with 50.0 and 25.0 mg, respectively, of elemental lead per kilogram of body weight (mg/kg BW of lead) using Pb(NO3)2 dissolved in distilled water. Group C was without Pb(NO3)2 as control. The ICP-Mass was used to determine the concentration of lead in blood, urine and tissues. The pharmacokinetic parameters were calculated by using WinNolin software. The unpaired-t test was used for statistical comparison. The T(subscript max) and t(subscript 1/2) in blood were 4.0±2.1 hr and 62.9±8.1 hr for group A, and 12.0±0.0 hr and 619.2±224.0 hr for group B, respectively. The C(subscript max) and AUC in blood were 958.0±97.2 μg/L and 34013.5±2602.9 μg•hr/L for group A, and 376.7±7.4 μg/L and 21257.3±1529.4 μg•hr/L for group B, respectively. These results indicated that the group A produced shorter in the T(subscript max) and t(subscript 1/2), and greater in the C(subscript max) and AUC seems to infer that the lead absorption (ie. accumulated in blood) and clearance from blood was quicker than that of group B significantly (P＜0.05). The T(subscript max) and t(subscript 1/2) in urine were 2.2±0.7 hr and 48.4±11.4 hr for group A, and 6.8±3.2 hr and 30.5±3.7 hr for group B, respectively. The maximum of elimination rate and AURC in urine were 67.68±5.14 μg/hr and 1610.56±195.80 μg•hr/L for group A, and 29.31±6.80 μg/hr and 523.75±94.55 μg•hr/L for group B, respectively. The volume of urine was 4480.4±342.6 mL for group A, and 2375.0±750.8 mL for group B, respectively. These results indicated that the group A in urine produced shorter in the T(subscript max), and higher in the max of elimination rate, AURC, and t(subscript 1/2) seems indicated that the excretion (ie. eliminated via urine) was faster than that of group B significantly (P＜0.05). There were no significant differences in complete blood count and urine routine analysis among the three groups. Also there were no significant differences in tissue lead concentration analyzed between group A and B, nonetheless there were significant differences between control group and lead ingested groups (P＜0.05). The highest lead concentration among those tissues was in the rib (24.093±3.478 μg/g for group A and 20.495±1.679 μg/g for group B); followed by descending order, the liver, hair, femur, kidney, spleen, muscle, heart, lung and brain of two lead-ingested groups but not in the control. In conclusion, this study demonstrated that a single oral administration of lead element produced a complex pharmacokinetics resemble to the orally repeated consumption of lead in swine. The possibility of the blood-compartment and the complex pharmacokinetics were discussed.

並列關鍵字

Pharmacokinetics ； Lead Nitrate ； Swine