Cambridge Isotope Laboratories Inc., Andover, MA 01830, USA.
J Parkinsons Dis. 2012;2(4):349-56. doi: 10.3233/JPD-012132.
Peripheral carbidopa (CD) levels directly impact on central dopamine (DA) production in Parkinson disease (PD) through extracerebral inhibition of dopa decarboxylase (AADC) resulting in an increase in levodopa (LD) bioavailability.
Recent data suggests that higher CD doses than those presently used in PD treatment may result in improved clinical response. Optimizing CD doses in individual patients may, therefore, result in ideal individualized treatment.
A single center, randomized, double-blind study was carried out recruiting 5 Parkinson’s disease (PD) patients already on LD/CD and 1 treatment näve PD patient using stable isotope labeled LD-1-¹³C as a substrate for a noninvasive breath test to evaluate individual AADC enzyme activity. Each patient was studied five times, receiving 200 mg LD-¹³C at each visit along with one of five randomized CD doses (0, 25, 50, 100 and 200 mg). The metabolite ¹³CO₂ in breath was measured for evaluating AADC enzyme activity and plasma metabolite levels for LD-¹³C and homovanillic acid (HVA) were measured for 4 hours.
HVA in plasma and ¹³CO₂ in breath are metabolic products of LD. We found a significant positive correlation of ¹³CO₂ DOB AUC0-240 with serum HVA AUC0-240 following the oral dose of LD-1-¹³C for all 5 doses of CD (r² = 0.9378). With increasing inhibition of AADC enzyme activity with CD, we observed an increase in the plasma concentration of LD.We found an inverse correlation of the 13CO2 DOB AUC with serum LD-¹³C AUC. Our studies indicate the optimal dose of CD for maximal suppression of AADC enzyme activity can be determined for each individual from ¹³CO₂ generation in breath.
The LD-breath test can be a useful noninvasive diagnostic tool for evaluation of AADC enzyme activity using the biomarker ¹³CO₂ in breath, a first step in personalizing CD doses for PD patients.
在外周给予卡比多巴（CD）可直接抑制多巴胺脱羧酶（AADC），从而减少脑外多巴胺（DA）的生成，提高左旋多巴（LD）的生物利用度。
近期数据表明，增加 PD 治疗中的 CD 剂量可能会改善临床疗效。因此，优化个体患者的 CD 剂量可能会实现理想的个体化治疗。
本研究为单中心、随机、双盲研究，共纳入 5 例正在接受 LD/CD 治疗的帕金森病（PD）患者和 1 例初始治疗的 PD 患者。使用稳定同位素标记的 LD-1-¹³C 作为非侵入性呼吸试验的底物，以评估个体 AADC 酶活性。每位患者接受 5 次研究，每次就诊时给予 200 mg LD-¹³C，并随机给予 5 种 CD 剂量（0、25、50、100 和 200 mg）。通过测量呼吸中的 ¹³CO₂评估 AADC 酶活性，同时测量 4 小时内的血浆代谢产物 LD-¹³C 和高香草酸（HVA）的水平。
HVA 和 ¹³CO₂ 是 LD 的代谢产物。我们发现，所有 5 种 CD 剂量下，口服 LD-1-¹³C 后，呼吸中 ¹³CO₂ DOB AUC0-240 与血清 HVA AUC0-240 呈显著正相关（r² = 0.9378）。随着 CD 对 AADC 酶活性的抑制增加，我们观察到 LD 的血浆浓度增加。我们发现 ¹³CO₂ DOB AUC 与血清 LD-¹³C AUC 呈负相关。我们的研究表明，通过呼吸中 ¹³CO₂ 的生成，可以为每位患者确定最大抑制 AADC 酶活性的 CD 最佳剂量，这是 PD 患者 CD 剂量个体化的第一步。
LD-呼吸试验可以作为一种有用的非侵入性诊断工具，通过呼吸中的生物标志物 ¹³CO₂ 评估 AADC 酶活性，为 PD 患者的 CD 剂量个体化提供依据。
