课件：药科大生物药剂学十多剂量给药.ppt

* LOGO (2) po * LOGO 与给药途经无关，蓄积系数(R) 仅由k1/2和t决定，不受X0与n和影响无关 * LOGO 10-5首剂量loading dose和维持剂量maintenance dose 回忆: iv constant infusion 4.32t1/2 C → 95% Css XL= Css×Vd Css k0 = Css×CL 1.简介 * LOGO nt = 4.32t1/2 → fss = 95% 1st t 2nd t 3rd t X0 → Cn → 全效 ? → 部分药效 ? → 无效 ? X0 t * LOGO 首剂量(Loading dose ) 维持剂量(Maintenance dose) ?负荷剂量, iv infusion 首剂量XL — 减少药物起效时间(即产生最小有效浓度MEC所需的时间) —在尽可能短的时间达到MEC；或在 1st t内就产生疗效同时 确保安全性 MEC 维持剂量 XM —在使用首剂量后, 采用(一系列)维持剂量来维持首剂量所产生的疗效 ? k0, iv infusion 解释: 使用XL在经过4t1/2后对由XM 所决定的平均稳态血浓无影响 * LOGO 2. 多剂量给药方案设计中首剂量 (XL)、维持剂量(XM) 和 t 的估算 (pages 244-248) XL, XM, t 有效性与安全性 (1) Method 1(pages 244-248) — 根据有效血浓范内的最小或目标血药浓度计算XL, XM, t minimum effective conc. (MEC) effective therapeutic conc. ≥ A. iv bolus injection → 疗效 在1st t内 minimum toxic conc. (MTC) ＜ * LOGO 在使用XL后，如果按照固定的t，反复使用 XM 假设 或令 * LOGO B. po dosing 如假设 因为 kel ＜ ka In summary, i) If t = t1/2, (iv and po) (t 7t1/2(ka)) * LOGO eg, a drug with a half-life of 6 hrs is given four time a day. * LOGO ii) If t t1/2, eg, t1/2 = 0.5 hr, t = 4 hr iii) If t t1/2, no resolution for XL eg, a drug with a half-life of 7 days is given once a day. A very long half-life may not be a good characteristic for a therapeutic agent. * LOGO 步骤： Step 1: 在药物治疗浓度范围内选择目标浓度并设定为平均稳态血药浓度 Step 2: 根据药物半衰期，选择给药间歇t, 如t ?为3-4、 4-6、 6-8、8-12、 或24 hrs时, 设定t = t1/2，即按照每日6次、4次、3次、2次及1次给药 Step 3: 根据方程式计算XM (F ?) If t1/2=6 hrs, t is set to 4 hrs (t ≠ t1/2) If t = t1/2 very short t1/2 t = 4 hrs, XL = XM THANK YOU SUCCESS * * 可编辑 * ie, the blood levels after the second, third, or nth dose will overlay the blood level attained after the (n-1)th dose. * For some drugs, such as hormone replacement therapy, a bioequivalence study may be performed in patients already maintained on the drug. In this case, a washout period would place the patient at substantial risk for being without drug therapy. Therefore, the patient continues on his or her own medication, and blood sampling is performed during a do