PHARMACOKINETICS
One of the main problems in therapeutics is the lack of awareness of just how much variability there is in drug disposition. In addition, many students have little insight into what the actual pharmacokinetic profile of the particular drug being prescribed actually looks like. Pharmacokinetics Visualizer hopes to be able to help overcome some of these difficulties.
The 7 scenarios here represent commonly encountered problems managed by doctors. The models shown here are loosely based on typical drugs used in these contexts. The variability shown are not specific for any particular drug but are empirically generated. They are however, not unusual for the drug examples.
Below are references for population pharmacokinetics of similar drugs. You can see for yourself how much variability there is in any population.
Brokjær, A., Kreilgaard, M., Olesen, A., Simonsson, U., Christrup, L., Dahan, A., & Drewes, A. (2015). Population pharmacokinetics of morphine and morphine-6-glucuronide following rectal administration – A dose escalation study. European Journal Of Pharmaceutical Sciences, 68, 78-86. doi: 10.1016/j.ejps.2014.12.004
Pierre, V., Johnston, C., Ferslew, B., Brouwer, K., & Gonzalez, D. (2017). Population pharmacokinetics of morphine in patients with nonalcoholic steatohepatitis (NASH) and healthy adults. CPT: Pharmacometrics & Systems Pharmacology, 6(5), 331-339. doi: 10.1002/psp4.12185
Abulfathi, A., Chirehwa, M., Rosenkranz, B., & Decloedt, E. (2018). Evaluation of the effectiveness of dose individualization to achieve therapeutic vancomycin concentrations. The Journal Of Clinical Pharmacology, 0(0), 1-6. doi: 10.1002/jcph.1254
Alqahtani, S., Alsultan, A., Alqattan, H., Eldemerdash, A., & Albacker, T. (2018). Population pharmacokinetic model for vancomycin used in open heart surgery: Model-based evaluation of standard dosing regimens. Antimicrobial Agents And Chemotherapy, AAC.00088-18. doi: 10.1128/aac.00088-18
Valitalo, P., Ranta, V., Hooker, A., Kokki, M., & Kokki, H. (2014). Population pharmacometrics in support of analgesics studies. Acta Anaesthesiologica Scandinavica, 58(2), 143-156. doi: 10.1111/aas.12253
Trocóniz, I., Tillmann, C., Liesenfeld, K., Schäfer, H., & Stangier, J. (2007). Population pharmacokinetic analysis of the new oral thrombin inhibitor dabigatran etexilate (BIBR 1048) in patients undergoing primary elective total hip replacement surgery. The Journal Of Clinical Pharmacology, 47(3), 371-382. doi: 10.1177/0091270006297228
Liesenfeld, K., Lehr, T., Dansirikul, C., Reilly, P., Connolly, S., & Ezekowitz, M. et al. (2011). Population pharmacokinetic analysis of the oral thrombin inhibitor dabigatran etexilate in patients with non-valvular atrial fibrillation from the RE-LY trial. Journal Of Thrombosis And Haemostasis, 9(11), 2168-2175. doi: 10.1111/j.1538-7836.2011.04498.x
Clemens, A., Haertter, S., Friedman, J., Brueckmann, M., Stangier, J., van Ryn, J., & Lehr, T. (2012). Twice daily dosing of dabigatran for stroke prevention in atrial fibrillation: a pharmacokinetic justification. Current Medical Research And Opinion, 28(2), 195-201. doi: 10.1185/03007995.2011.654109
Gotfried, M. (2003). Steady-state plasma and bronchopulmonary characteristics of clarithromycin extended-release tablets in normal healthy adult subjects. Journal Of Antimicrobial Chemotherapy, 52(3), 450-456. doi: 10.1093/jac/dkg355
Gong, I., Schwarz, U., Crown, N., Dresser, G., Lazo-Langner, A., & Zou, G. et al. (2011). Clinical and genetic determinants of warfarin pharmacokinetics and pharmacodynamics during treatment initiation. Plos ONE, 6(11), e27808. doi: 10.1371/journal.pone.0027808
Kubo, K., Ohara, M., Tachikawa, M., Cavallari, L., Lee, M., & Wen, M. et al. (2016). Population differences in S-warfarin pharmacokinetics among African Americans, Asians and whites: Their influence on pharmacogenetic dosing algorithms. The Pharmacogenomics Journal, 17(6), 494-500. doi: 10.1038/tpj.2016.57
Abduljalil, K., Kinzig, M., Bulitta, J., Horkovics-Kovats, S., Sorgel, F., Rodamer, M., & Fuhr, U. (2009). Modeling the autoinhibition of clarithromycin metabolism during repeated oral administration. Antimicrobial Agents And Chemotherapy, 53(7), 2892-2901. doi: 10.1128/aac.01193-08