Updated CYP2C8 Qualification package for OSP9 release (#6)

* Updated CYP2C8 Qualification package for OSP9 release * Update README.md
Open-Systems-Pharmacology · Jun 18, 2020 · 4823195 · 4823195
1 parent 9135e3a
commit 4823195
Show file tree

Hide file tree

Showing 9 changed files with 10 additions and 562 deletions.
diff --git a/Input/Content/Paclitaxel_adults.md b/Input/Content/Paclitaxel_adults.md
diff --git a/Input/Content/Paclitaxel_children.md b/Input/Content/Paclitaxel_children.md
diff --git a/Input/Content/Paclitaxel_diagnostics.md b/Input/Content/Paclitaxel_diagnostics.md
diff --git a/Input/Content/Section1.md b/Input/Content/Section1.md
@@ -24,10 +24,9 @@ The CYP2C8 ontogeny function is reported by Upreti et al. [[3](#reference)] and
 
 ### Qualification of **CYP2C8 enzyme ontogeny**
 
-To qualify the OSP suite for the pediatric translation of the pharmacokinetics of new drugs that are metabolized by CYP2C8, the following set of probe substances was included:
+To qualify the OSP suite for the pediatric translation of the pharmacokinetics of new drugs that are metabolized by CYP2C8, the following probe substance was included:
 
-- Montelukast [[4](#reference)]
-- Paclitaxel [[5](#reference)]
+- Montelukast [[5](#reference)]
 
 ### References
 
@@ -41,5 +40,3 @@ To qualify the OSP suite for the pediatric translation of the pharmacokinetics o
 
 [5] [Montelukast-Model, Whole-body PBPK model of Montelukast. https://github.com/Open-Systems-Pharmacology/Montelukast-Model](https://github.com/incei/Montelukast-Model)
 
-[6] [Paclitaxel-Model, Whole-body PBPK model of Paclitaxel. https://github.com/Open-Systems-Pharmacology/Paclitaxel-Model](https://github.com/incei/Paclitaxel-Model)
-
diff --git a/Input/Content/Section2.md b/Input/Content/Section2.md
@@ -1,4 +1,4 @@
 ## Evaluation of Adult PBPK models
 
-The PBPK models of **montelukast** and **paclitaxel** were developed with clinical pharmacokinetic data covering at least administrations given in children. Plasma concentrations following intravenous administration, oral administration, multiple dose application, fractions excreted to urine or bile and other clinical measurements were included for model development whenever available. 
+The PBPK model of **montelukast** was developed with clinical pharmacokinetic data covering at least administrations given in children. Plasma concentrations following intravenous administration, oral administration, multiple dose application, fractions excreted to urine or bile and other clinical measurements were included for model development whenever available. 
 
diff --git a/Input/PK-Parameters.csv b/Input/PK-Parameters.csv
@@ -59,22 +59,6 @@ ID,Study,Reference,Grouping,Analyte,t0,tend,t Unit,AUC Avg,AUC AvgUnit,AUC AvgTy
 5292,Zhao 1997,https://www.ncbi.nlm.nih.gov/pubmed/9429741,MD 10mg FCT,Montelukast,0,24,h,3624,ng*h/mL,geo. mean,1258,ng*h/mL,geo. SD,AUC_inf,541.5,ng/mL,geom.mean,172.6,ng/mL,arith. SD,Cmax,,,,,,,,,
 5293,Fey 2014,https://www.ncbi.nlm.nih.gov/pubmed/25250173,4mg PO granules (Sandoz),Montelukast,0,36,h,1083,ng*h/mL,arith. Mean,293.88,ng*h/mL,arith. SD,AUC_tend,178.04,ng/mL,arith. mean,41.58,ng/mL,arith. SD,Cmax,,,,,,,,,
 5294,Fey 2014,https://www.ncbi.nlm.nih.gov/pubmed/25250173,4mg PO granules (Singular),Montelukast,0,36,h,1112.84,ng*h/mL,arith. Mean,309.13,ng*h/mL,arith. SD,AUC_tend,196.04,ng/mL,arith. mean,53.25,ng/mL,arith. SD,Cmax,,,,,,,,,
-5310,Doz 2001,https://www.ncbi.nlm.nih.gov/pubmed/11237379,Diamond Black,Paclitaxel,0,3,h,0.0708,mmol*h/L,arith. Mean,15.7,�mol*h/L,arith. SD,AUC_tau,22.4,�mol/L,arith. mean,6.5,�mol/L,arith. SD,Cmax,4.99,L/h/m2,arith.mean,0.99,L/h/m2,arith. SD,CLiv,AUC AvgType changed unit from � to milli by dividing with 1000,
-5311,Horton 2008,https://www.ncbi.nlm.nih.gov/pubmed/17668866,430mg/m2,Paclitaxel,0,48,h,0.0224,mg*h/mL,arith. Mean,7.4,�g*h/mL,arith. SD,AUC_tau,0.87,�g/L,arith. mean,0.28,�g/L,arith. SD,Cmax,21,L/h/m2,arith.mean,9.5,L/h/m2,arith. SD,CLiv,AUC AvgType changed unit from � to milli by dividing with 1000,
-5312,Sonnichsen 1994,https://www.ncbi.nlm.nih.gov/pubmed/7907130,2.3-22.8y,Paclitaxel,0,24,h,0.03,mmol*h/L,median,,,,,,,,,,,,135,mL/min/m2,arith.mean,,,,CLiv,"Clearance based on POP-pk model, auc based on boxplot",
-5313,Diamond 2015,https://www.ncbi.nlm.nih.gov/pubmed/25895965,80mgm2,Paclitaxel,0,,,,,,,,,,,,,,,,,,,,,,,,,
-5314,Huizing 1993,https://www.ncbi.nlm.nih.gov/pubmed/7901342,135mgm2 24h,Paclitaxel,0,,,,,,,,,,,,,,,,,,,,,,,,,
-5315,Huizing 1993,https://www.ncbi.nlm.nih.gov/pubmed/7901342,135mgm2 3h,Paclitaxel,0,,,,,,,,,,,,,,,,,,,,,,,,,
-5316,Huizing 1993,https://www.ncbi.nlm.nih.gov/pubmed/7901342,175mgm2 24h,Paclitaxel,0,,,,,,,,,,,,,,,,,,,,,,,,,
-5317,Huizing 1993,https://www.ncbi.nlm.nih.gov/pubmed/7901342,175mgm2 3h,Paclitaxel,0,,,,,,,,,,,,,,,,,,,,,,,,,
-5318,Huizing 1995,https://www.ncbi.nlm.nih.gov/pubmed/8664192,250mgm2 3h,Paclitaxel,0,,,,,,,,,,,,,,,,,,,,,,,,,
-5319,Ibrahim 2002,https://www.ncbi.nlm.nih.gov/pubmed/12006516,135mgm2 3h,Paclitaxel,0,,,,,,,,,,,,,,,,,,,,,,,,,
-5320,Ibrahim 2002,https://www.ncbi.nlm.nih.gov/pubmed/12006516,135mgm2 0.5h,Paclitaxel,0,,,,,,,,,,,,,,,,,,,,,,,,,
-5321,Ibrahim 2002,https://www.ncbi.nlm.nih.gov/pubmed/12006516,200mgm2 0.5h,Paclitaxel,0,,,,,,,,,,,,,,,,,,,,,,,,,
-5322,Ibrahim 2002,https://www.ncbi.nlm.nih.gov/pubmed/12006516,300mgm2 0.5h,Paclitaxel,0,,,,,,,,,,,,,,,,,,,,,,,,,
-5323,Ibrahim 2002,https://www.ncbi.nlm.nih.gov/pubmed/12006516,375mgm2 0.5h,Paclitaxel,0,,,,,,,,,,,,,,,,,,,,,,,,,
-5324,Sparreboom 2005,https://www.ncbi.nlm.nih.gov/pubmed/15930349,260mgm2 0.5h,Paclitaxel,0,,,,,,,,,,,,,,,,,,,,,,,,,
-5325,Sparreboom 2005,https://www.ncbi.nlm.nih.gov/pubmed/15930349,175mgm2 3h,Paclitaxel,0,,,,,,,,,,,,,,,,,,,,,,,,,
 5403,Friesen 2004,https://www.ncbi.nlm.nih.gov/pubmed/15076638,Mean ,Montelukast,0,12,h,4387.2,ng*h/mL,geo. mean,1485.1,ng*h/mL,geo.SD,AUC_inf,,,,,,,,,,,,,,,,
 5404,Knorr 2001,https://www.ncbi.nlm.nih.gov/pubmed/11402629,2-5y,Montelukast,0,24,h,2721,ng*h/mL,geo. mean,164,ng*h/mL,geo.SD,AUC_inf,,,,,,,,,,,,,,,,
 5405,Knorr 1999,https://www.ncbi.nlm.nih.gov/pubmed/10434229,9-14y GT45kg,Montelukast,0,24,h,3528,ng*h/mL,geo. mean,1883,ng*h/mL,geo.SD,AUC_inf,526,ng/mL,arith. mean,413,ng/mL,arith. SD,Cmax,,,,,,,,,
@@ -88,18 +72,4 @@ ID,Study,Reference,Grouping,Analyte,t0,tend,t Unit,AUC Avg,AUC AvgUnit,AUC AvgTy
 5413,Cheng 1996,https://www.ncbi.nlm.nih.gov/pubmed/8692739,18mg IV male,Montelukast,0,24,h,,,,,,,,,,,,,,,40.2,mL/min,harmonic mean,6.4,mL/min,Jacknife SD,CLiv,,
 5414,Cheng 1996,https://www.ncbi.nlm.nih.gov/pubmed/8692739,9mg IV Female,Montelukast,0,24,h,,,,,,,,,,,,,,,47.6,mL/min,harmonic mean,16,mL/min,Jacknife SD,CLiv,,
 5415,Cheng 1996,https://www.ncbi.nlm.nih.gov/pubmed/8692739,10mg PO Female,Montelukast,0,24,h,2270,ng*h/mL,Harmonic mean,919,ng*h/mL,Jacknife SD,AUC_tau,350,ng/mL,Harmonic mean,161,ng/mL,Jacknife SD,Cmax,,,,,,,,,
-5416,Cheng 1996,https://www.ncbi.nlm.nih.gov/pubmed/8692739,10mg PO male,Montelukast,0,24,h,2441,ng*h/mL,Harmonic mean,441,ng*h/mL,Jacknife SD,AUC_tau,385,ng/mL,Harmonic mean,85,ng/mL,Jacknife SD,Cmax,,,,,,,,,
-5419,Doz 2001,https://www.ncbi.nlm.nih.gov/pubmed/11237379,Diamond white,Paclitaxel,0,3,h,0.0708,mmol*h/L,arith. Mean,15.7,�mol*h/L,arith. SD,AUC_tau,22.4,�mol/L,arith. mean,6.5,�mol/L,arith. SD,Cmax,4.99,L/h/m2,arith.mean,0.99,L/h/m2,arith. SD,CLiv,AUC AvgType changed unit from � to milli by dividing with 1000,
-5420,Doz 2001,https://www.ncbi.nlm.nih.gov/pubmed/11237379,Square black,Paclitaxel,0,3,h,0.0708,mmol*h/L,arith. Mean,15.7,�mol*h/L,arith. SD,AUC_tau,22.4,�mol/L,arith. mean,6.5,�mol/L,arith. SD,Cmax,4.99,L/h/m2,arith.mean,0.99,L/h/m2,arith. SD,CLiv,AUC AvgType changed unit from � to milli by dividing with 1000,
-5421,Doz 2001,https://www.ncbi.nlm.nih.gov/pubmed/11237379,Square white,Paclitaxel,0,3,h,0.0708,mmol*h/L,arith. Mean,15.7,�mol*h/L,arith. SD,AUC_tau,22.4,�mol/L,arith. mean,6.5,�mol/L,arith. SD,Cmax,4.99,L/h/m2,arith.mean,0.99,L/h/m2,arith. SD,CLiv,AUC AvgType changed unit from � to milli by dividing with 1000,
-5422,Doz 2001,https://www.ncbi.nlm.nih.gov/pubmed/11237379,Triangle black,Paclitaxel,0,3,h,0.0708,mmol*h/L,arith. Mean,15.7,�mol*h/L,arith. SD,AUC_tau,22.4,�mol/L,arith. mean,6.5,�mol/L,arith. SD,Cmax,4.99,L/h/m2,arith.mean,0.99,L/h/m2,arith. SD,CLiv,AUC AvgType changed unit from � to milli by dividing with 1000,
-5423,Doz 2001,https://www.ncbi.nlm.nih.gov/pubmed/11237379,Triangle white,Paclitaxel,0,3,h,0.0708,mmol*h/L,arith. Mean,15.7,�mol*h/L,arith. SD,AUC_tau,22.4,�mol/L,arith. mean,6.5,�mol/L,arith. SD,Cmax,4.99,L/h/m2,arith.mean,0.99,L/h/m2,arith. SD,CLiv,AUC AvgType changed unit from � to milli by dividing with 1000,
-5424,Horton 2008,https://www.ncbi.nlm.nih.gov/pubmed/17668866,250mgm2,Paclitaxel,0,48,h,0.01,mg*h/mL,arith. Mean,4.1,�g*h/mL,arith. SD,AUC_tau,0.38,�g/ml,arith. mean,0.13,�g/L,,Cmax,28,L/h/m2,arith.mean,11,L/h/m2,arith. SD,CLiv,AUC AvgType changed unit from � to milli by dividing with 1000,
-5425,Horton 2008,https://www.ncbi.nlm.nih.gov/pubmed/17668866,300mgm2,Paclitaxel,0,48,h,0.0164,mg*h/mL,arith. Mean,9.6,�g*h/mL,arith. SD,AUC_tau,0.65,�g/ml,arith. mean,0.4,�g/L,,Cmax,26,L/h/m2,arith.mean,22,L/h/m2,arith. SD,CLiv,AUC AvgType changed unit from � to milli by dividing with 1000,
-5426,Horton 2008,https://www.ncbi.nlm.nih.gov/pubmed/17668866,360mgm2,Paclitaxel,0,48,h,0.0236,mg*h/mL,arith. Mean,15.3,�g*h/mL,arith. SD,AUC_tau,0.93,�g/ml,arith. mean,0.68,�g/L,,Cmax,19,L/h/m2,arith.mean,13,L/h/m2,arith. SD,CLiv,AUC AvgType changed unit from � to milli by dividing with 1000,
-5427,Horton 2008,https://www.ncbi.nlm.nih.gov/pubmed/17668866,400mgm2,Paclitaxel,0,48,h,0.0186,mg*h/mL,individual,,,,AUC_tau,0.74,�g/ml,individual,,,,Cmax,23,L/h/m2,Individual,,,,CLiv,AUC AvgType changed unit from � to milli by dividing with 1000,
-5428,Horton 2008,https://www.ncbi.nlm.nih.gov/pubmed/17668866,500mgm2,Paclitaxel,0,48,h,0.036,mg*h/mL,arith. Mean,12,�g*h/mL,arith. SD,AUC_tau,1.3,�g/ml,arith. mean,0.7,�g/L,,Cmax,15,L/h/m2,arith.mean,6,L/h/m2,arith. SD,CLiv,AUC AvgType changed unit from � to milli by dividing with 1000,
-5429,Doz 2001,https://www.ncbi.nlm.nih.gov/pubmed/11237379,240mgm2,Paclitaxel,0,3,h,0.0338,mmol*h/L,arith. Mean,4.8,�mol*h/L,arith. SD,AUC_tau,8.3,�mol/L,arith. mean,2.1,�mol/L,arith. SD,Cmax,8.48,L/h/m2,arith.mean,1.24,L/h/m2,arith. SD,CLiv,AUC AvgType changed unit from � to milli by dividing with 1000,
-5430,Doz 2001,https://www.ncbi.nlm.nih.gov/pubmed/11237379,290mgm2,Paclitaxel,0,3,h,0.0708,mmol*h/L,arith. Mean,15.7,�mol*h/L,arith. SD,AUC_tau,22.4,�mol/L,arith. mean,6.5,�mol/L,arith. SD,Cmax,4.66,L/h/m2,arith.mean,0.99,L/h/m2,arith. SD,CLiv,AUC AvgType changed unit from � to milli by dividing with 1000,
-5431,Doz 2001,https://www.ncbi.nlm.nih.gov/pubmed/11237379,350mgm2,Paclitaxel,0,3,h,0.1567,mmol*h/L,arith. Mean,75.7,�mol*h/L,arith. SD,AUC_tau,40.2,�mol/L,arith. mean,17.8,�mol/L,arith. SD,Cmax,3.39,L/h/m2,arith.mean,1.61,L/h/m2,arith. SD,CLiv,AUC AvgType changed unit from � to milli by dividing with 1000,
-5432,Doz 2001,https://www.ncbi.nlm.nih.gov/pubmed/11237379,420mgm2,Paclitaxel,0,3,h,0.1796,mmol*h/L,arith. Mean,0.1,�mol*h/L,arith. SD,AUC_tau,38.9,�mol/L,arith. mean,4.9,�mol/L,arith. SD,Cmax,2.74,L/h/m2,arith.mean,0.01,L/h/m2,arith. SD,CLiv,AUC AvgType changed unit from � to milli by dividing with 1000,
+5416,Cheng 1996,https://www.ncbi.nlm.nih.gov/pubmed/8692739,10mg PO male,Montelukast,0,24,h,2441,ng*h/mL,Harmonic mean,441,ng*h/mL,Jacknife SD,AUC_tau,385,ng/mL,Harmonic mean,85,ng/mL,Jacknife SD,Cmax,,,,,,,,,