Laboratory and clinical outcomes of pharmacogenetic vs. clinical protocols for warfarin initiation in orthopedic patients.
Laboratory and clinical outcomes of pharmacogenetic vs. clinical protocols for warfarin initiation in orthopedic patients.
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DOI：
10.1111/j.1538-7836.2008.03095.x
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发表时间：
2008-10
期刊：
影响因子：
--
通讯作者：
Gage BF
中科院分区：
文献类型：
--
作者：
Lenzini PA;Grice GR;Milligan PE;Dowd MB;Subherwal S;Deych E;Eby CS;King CR;Porche-Sorbet RM;Murphy CV;Marchand R;Millican EA;Barrack RL;Clohisy JC;Kronquist K;Gatchel SK;Gage BF
Warfarin通常用于预防和治疗骨科手术后的血栓栓塞。在开始华法林治疗期间，国际标准化比值（INR）值超出范围和不良事件很常见。在开始华法林治疗的骨科患者中，我们开发并前瞻性验证了药物遗传学和临床剂量优化算法，以修订治疗4天后的估计治疗剂量。药物遗传学算法使用细胞色素P450（CYP）2C 9基因型、吸烟状态、围手术期失血量、肝脏疾病、INR值和给药史来预测治疗剂量。衍生队列中的R2为82%（N = 86），前瞻性使用时为70%（N = 146）。使用INR值和剂量史预测治疗剂量的临床算法的R2在推导队列（N = 178）中为57%，在前瞻性验证队列（N = 146）中为48%。在一个月的前瞻性随访中，药物遗传学队列中治疗范围内花费的时间百分比高7%（95% CI：2.7%-11.7%）。药物遗传学队列中实验室或临床不良事件的风险也显著降低（风险比0.54; 95% CI：0.29-0.97）。华法林剂量调整，包括基因型和临床变量后，四个华法林剂量是准确的。在这项非随机前瞻性研究中，药物遗传学剂量优化与治疗范围内花费的时间更多和实验室或临床不良事件较少相关。为了促进基因指导的华法林剂量，我们创建了一个非营利网站，www.WarfarinDosing.org。
Warfarin is commonly prescribed for prophylaxis and treatment of thromboembolism after orthopedic surgery. During warfarin initiation, out-of-range International Normalized Ratio (INR) values and adverse events are common. In orthopedic patients beginning warfarin therapy, we developed and prospectively validated pharmacogenetic and clinical dose refinement algorithms to revise the estimated therapeutic dose after 4 days of therapy. The pharmacogenetic algorithm used the cytochrome P450 (CYP) 2C9 genotype, smoking status, perioperative blood loss, liver disease, INR values, and dose history to predict the therapeutic dose. The R2 was 82% in a derivation cohort (N = 86), and 70% when used prospectively (N = 146). The R2 of the clinical algorithm that used INR values and dose history to predict the therapeutic dose was 57% in a derivation cohort (N = 178), and 48% in a prospective validation cohort (N = 146). In one month of prospective follow-up, the percent time spent in the therapeutic range was 7% higher (95% CI: 2.7%–11.7%) in the pharmacogenetic cohort. The risk of laboratory or clinical adverse event was also significantly reduced in the pharmacogenetic cohort (Hazard Ratio 0.54; 95% CI: 0.29–0.97). Warfarin dose adjustments that incorporate genotype and clinical variables available after four warfarin doses are accurate. In this non-randomized, prospective study, pharmacogenetic dose refinements were associated with more time spent in the therapeutic range and fewer laboratory or clinical adverse events. To facilitate gene-guided warfarin dosing we created a non-profit website, www.WarfarinDosing.org.
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影响因子：
7.5
作者：
Odén, A;Fahlén, M;Hart, RG
通讯作者：
Hart, RG
影响因子：
20.3
作者：
Sconce, EA;Khan, TI;Kamali, F
通讯作者：
Kamali, F
影响因子：
4
作者：
Linder, MW;Looney, S;Valdes, R
通讯作者：
Valdes, R
DOI：
10.1007/bf01065653
发表时间：
1985-01-01
期刊：
JOURNAL OF PHARMACOKINETICS AND BIOPHARMACEUTICS
影响因子：
--
作者：
MUNGALL, DR;LUDDEN, TM;CRAWFORD, MH
通讯作者：
CRAWFORD, MH
影响因子：
6.7
作者：
Limdi, Na;McGwin, G.;Acton, R. T.
通讯作者：
Acton, R. T.