Interdigestive Migrating Motility Complex(IMMC)Phase I:Absence of motor activityPhase II:Irregular contraction processPhase III:Rhythmic contractions of highamplitudePhase IV:Transitional period corresponding to areduction in intensity and frequencyof contractionsItohZet al (1982).Gastroenterology1982;82:694-700
Interdigestive Migrating Motility Complex (IMMC) Phase I: Absence of motor activity Phase II: Irregular contraction process Phase III: Rhythmic contractions of high amplitude Phase IV: Transitional period corresponding to a reduction in intensity and frequency of contractions Itoh Z et al (1982). Gastroenterology 1982; 82: 694-700
Modified two-portion absorption model雨部分吸收模型K (t≥T)XiK12KaXpGAK212K1K,(t≥T2)
Modified two-portion absorption model 兩部分吸收模型 X1 X2 GA Xc Xp K1 (tT1 ) K2 (tT2 ) Ka K10 K12 K21
SubiectA1aSubjectA220002000150015001000100050050000026264804810121012time (hour)time (hour)ee2000Subject A42000SubjectA3150015001000100050050000602481012024681012time (hour)time (hour)SubjectA6SubjectA5e20002000150015001000100050050000082610124602481012time (hour)time (hour)Curvefittingforranitidineconcentrationdatawithdoublepeaks
Curve fitting for ranitidine concentration data with double peaks Subject A3 0 500 1000 1500 2000 0 2 4 6 8 10 12 time (hour) concentration (ng/ml) Subject A5 0 500 1000 1500 2000 0 2 4 6 8 10 12 time (hour) concentration (ng/ml) Subject A4 0 500 1000 1500 2000 0 2 4 6 8 10 12 time (hour) concentration (ng/ml) Subject A1 0 500 1000 1500 2000 0 2 4 6 8 10 12 time (hour) concentration (ng/ml) Subject A6 0 500 1000 1500 2000 0 2 4 6 8 10 12 time (hour) concentration (ng/ml) Subject A2 0 500 1000 1500 2000 0 2 4 6 8 10 12 time (hour) concentration (ng/ml)
subject B2SubjectB120004000(u/6u)(/bu)20001000000261012:4.8024681012time (hour)time (hour)Subject B3Subject B46000(w/bu)3000(w/bu)200040002000100000060262410124812810time (hour)time (hour)SubjectB5Subject B62000(u/6u)-2000(/6u)1000100000026810124024681012time (hour)time (hour)Curve fittingforranitidine concentrationdata with apparent singlepeak
Subject B1 0 2000 4000 0 2 4 6 8 10 12 time (hour) concentration (ng/ml) Subject B3 0 2000 4000 6000 0 2 4 6 8 10 12 time (hour) concentration (ng/ml) Subject B4 0 1000 2000 3000 0 2 4 6 8 10 12 time (hour) concentration (ng/ml) Subject B5 0 1000 2000 0 2 4 6 8 10 12 time (hour) concentration (ng/ml) Subject B6 0 1000 2000 0 2 4 6 8 10 12 time (hour) concentration (ng/ml) subject B2 0 1000 2000 0 2 4 6 8 10 12 t ime (hour) concentration (ng/ml) Curve fitting for ranitidine concentration data with apparent single peak
Comparisonof ranitidinePKparametersobtained bythe modified two-portion absorptionmodel andnon-compartmental analysisparameternon-compartmentalanalysismodifiedabsorptionmodelGroupA (n=6)Tmax1 (h)1.20±0.361.36±0.39Tmax2 (h)3.42 ±0.662.97 ± 0.64Cmax1 (μg-ml)0.58 ± 0.160.63 ± 0.191.07 ± 0.271.22±0.29Cmax2 (μg-ml)AUCo-o (μg·homl1)5.62 ± 1.235.62 ± 1.34CL/F (Lh-1)55.53 ±12.4056.17 ± 14.42GroupB(n=6)Tmax (h)1.90 ± 0.421.84 ± 0.54Cmax (μgoml)2.07±1.362.05±1.34AUCo-o (μg·homl-1)6.22±1.946.31± 1.92CL/F (Lh-")52.20±16.3351.50±16.35
Comparison of ranitidine PK parameters obtained by the modified twoportion absorption model and non-compartmental analysis parameter non-compartmental analysis modified absorption model Group A (n=6) Tmax1 (h) 1.20 0.36 1.36 0.39 Tmax2 (h) 3.42 0.66 2.97 0.64 Cmax1 (g•ml) 0.58 0.16 0.63 0.19 Cmax2 (g•ml) 1.07 0.27 1.22 0.29 AUC0- (g•h•ml-1) 5.62 1.23 5.62 1.34 CL/F (L•h -1) 55.53 12.40 56.17 14.42 Group B (n=6) Tmax (h) 1.90 0.42 1.84 0.54 Cmax (g•ml) 2.07 1.36 2.05 1.34 AUC0- (g•h•ml-1) 6.22 1.94 6.31 1.92 CL/F (L•h -1) 52.20 16.33 51.50 16.35