Wooding-Scott R A, Darling I M, Slaughter R L
Department of Pharmacy Practice, College of Pharmacy, Ohio State University.
DICP. 1989 Dec;23(12):999-1004. doi: 10.1177/106002808902301210.
Individualized quinidine dosing through the assessment of serum concentrations is warranted because of the wide variability observed in its pharmacokinetic behavior and its reported narrow therapeutic index. The free fraction of quinidine also varies widely. Thus the development of procedures that could be widely used to determine quinidine free concentrations would be highly desirable. It was the purpose of this study to evaluate several procedures available to determine total serum quinidine concentrations (rate nephelometry [ICS], homogenous enzyme immunoassay [EMIT], and high-performance liquid chromatography [HPLC]). Furthermore, in samples from 46 patients, equilibrium dialysis and ultrafiltration procedures were compared for their ability to estimate quinidine free fraction. Finally, unbound concentrations of quinidine were compared using a modified EMIT procedure and a standard HPLC method to quantitate quinidine in ultrafiltrates from patient samples. For the measurement of total quinidine concentrations, reasonable agreement was seen when EMIT and ICS systems were compared with HPLC (ICS = 1.03.HPLC + 0.96, r = 0.93; EMIT = 1.08.HPLC + 0.38, r = 0.93) The mean errors, however, for these procedures were high (ICS +70 percent, range +7 to +233 percent; EMIT +35 percent, range 0 to 110 percent). Quinidine free fractions (QFF) determined by equilibrium dialysis (E) and ultrafiltration (U) showed good agreement (QFF(U) = 1.11.QFF(E) +0.0; r = 0.96). Unbound quinidine concentration determined by EMIT analysis of ultrafiltrate substantially overestimated the values obtained by HPLC analysis (mean error by EMIT 104 +/- 59 percent). It is concluded that HPLC is the method of choice for determining both total and unbound serum quinidine concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)
鉴于奎尼丁药代动力学行为存在广泛变异性且其治疗指数较窄，通过评估血清浓度进行个体化给药是必要的。奎尼丁的游离分数也有很大差异。因此，开发可广泛用于测定奎尼丁游离浓度的方法将非常理想。本研究的目的是评估几种可用于测定血清总奎尼丁浓度的方法（速率散射比浊法[ICS]、均相酶免疫测定法[EMIT]和高效液相色谱法[HPLC]）。此外，在46例患者的样本中，比较了平衡透析和超滤法估算奎尼丁游离分数的能力。最后，使用改良的EMIT法和标准HPLC法比较患者样本超滤液中奎尼丁的未结合浓度。对于总奎尼丁浓度的测定，将EMIT和ICS系统与HPLC比较时，结果有合理的一致性（ICS = 1.03×HPLC + 0.96，r = 0.93；EMIT = 1.08×HPLC + 0.38，r = 0.93）。然而，这些方法的平均误差较高（ICS为 +70%，范围为 +7%至 +233%；EMIT为 +35%，范围为0至110%）。通过平衡透析（E）和超滤（U）测定的奎尼丁游离分数（QFF）显示出良好的一致性（QFF(U) = 1.11×QFF(E) +0.0；r = 0.96）。通过超滤液的EMIT分析测定的未结合奎尼丁浓度大大高估了通过HPLC分析获得的值（EMIT的平均误差为104±59%）。结论是，HPLC是测定血清总奎尼丁浓度和未结合奎尼丁浓度的首选方法。（摘要截断于250字）
