One compartmental i.v. infusion

One compartmental iv infusion seminar

1. PRESENTED BY- MR. DEBASHIS PUROHIT M.PHARM,2 nd SEMESTER (INDUSTRIALPHARMACY) DATE-16 th May,2018 Regd no-1761617004 SCHOOL OF PHARMACEUTICALSCIENCES, SIKSHA ‘O’ ANUSANDHAN (DEEMED TO BE UNIVERSITY), BHUBANESWAR,ODISHA SUBJECT -ADVANCED BIOPHARMACEUTICS AND PHARMACOKINETICS TOPIC -ONE COMPARTMENTAL I.V. INFUSION M.PHARM,2 nd SEMeSTER SEMINAR

2. INTRODUCTION - A compartment is a group of tissues with similar blood flow and drug affinity . One compartment open model is generally used to describe plasma levels administration of a single dose of a drug . Assumptions - Drugs may be administered to patients by various routes including oral, topical or parenteral routes of administration. Drugs moves dynamically in and out this compartment. Rate of input is greater then the elimination.

3. Limitations – It does not assume that the drug conc. in plasma is equal to that in other body fluids . The term open indicates that the input and output are unidirectional and that the drug can be eliminated from the body completely. Depending upon the rate of input,one compartmental open models are Classified in to- Iv bolus Iv infusion Extra vascular administration ,zero order Extra vascular administration ,First order

4. One Compartmental I.V. INFUSION [1] - Drug administration through the intravenous route at a constant rate over a determined time interval . On starting the infusion, there is no drug in the body and therefore, no elimination.Thus,the rate of elimination will rise untill it matches the rate of infusion.The amount of drug in the body is then constant and is said to have reached a steady state.

5. F actors affecting the steady state plasma drug concentrations [1] - Infusion rate (Ro): The steady state drug concentration is proportional to the infusion rate. Thus, a higher infusion rate will result in a higher steady state plasma drug concentration. Clearance: Higher clearance of the drug will result in lower plasma drug concentration at steady state.

6. The model can be represented as follows [1 ] - Plasma concentration-time profile for a drug given by constant rate i.v. infusion. Css =R ÷C L Css =Drug plasma conc. at steady state. C L =  Clearance R =Infusion rates

7. ( T he two curves indicate different infusion rates Ro and 2Ro for the same drug). = Drug plasma concentration at steady state. ( Figure-1 Plasma conc. Vs time curve for a given drug)

8. Knudsen K. etal ; Central nervous and cardiovascular effects of I.V. infusions of Ropivacaine , Bupivacaine and placebo in volunteers [2] . The objective of the study is to observe the comparison in CNS symptoms and change in electrocardiography & electrophysiology during IV infusion of Ropivacaine , Bupivacaine and placebo. Acute tolerance of IV infusion of 10mg/min was studied in a crossover, randomized, double-blinded study in 12 volunteers previously acquainted with Lignocaine. The tolerance of Ropivacaine was in 9 subjects and tolerance of Bupivacaine was in 3 subjects. The 95% confidence limits for difference in dosage of Ropivacaine and Bupivacaine were upto 30mg and 7mg respectively. RESEARCH ARTICLE-1

9. Tolerance of local anaesthetics has been assessed in volunteers in given concentrations. In genereal the threshold decreases with increase of the infusion rate as the plasma concentration is directly proportional to the dose and inversely proportional to cardiac output and infusion rate. In this study the rate of infusion was 10mg/min. was compromises between the maximum dose allowed and time within which the short lasting effects could be recorded. CONCLUSION-

10. Patel C.R. etal ; Effect of intravenous infusion of dexmedetomidine on perioperative haemodynamic changes and post operative recovery: A study with entropy analysis [3] . Dexmedetomidine is an -2 receptor agonist which is used as an adjuvant in general anaesthesia attenuates to various stress response to various noxious stimuli, maintain perioperative haemodynamic stability and causes sedation without causes significant respiratory depression prospectively. In this study 60 patients were selected and divided into 2 groups and the first groups was treated with Fentanyl 2g/kg and the second group was introduced to Dexmedetomidine 1g/kg. Sevoflurane was used in both groups as an inhalation agent. The haemodynamic variables and entropy (response entropy and state entropy) was monitored and recorded continously . RESEARCH ARTICLE-2

11. Dexmedetomidine,when administered as a pre- anaesthetic medication and intraperative infusion, attenuates stress response to various noxious stimuli and maintain haemodynamic stability. Dexmedetodine’s sedative property delays prospective recovery, thus continuous monitoring is essential for first few hours of prospective period. Conclusion -

12. RESEARCH ARTICLE-3 Dimitrova D. et al; Pharmacokinetics of Dicloxacillin sodium after Intravenous and Intramuscular administration to sheep. [4] The disposition of dicloxacillin sodium, given intravenous (i.v.) or intramuscular (i.m.) at 25 mg/kg body weight was studied in a total of 6 locally-bred sheep, age between 2-3 years and weighing between 40 and 45 kg. Data were analyzed by compartmental and non-compartmental models. The intravenous and intramuscular serum concentration curves were best described by one-compartment pharmacokinetic open model.

13. (Figure 1- Serum concentrations of dicloxacillin after i.v . and i.m. administration in sheep at a dose 25 mg/kg of body weight) Results and discussion-

14. Table 1 -Pharmacokinetic parameters ( Mean±SEM ) after i.v. infusion administration of dicloxacillin at a dose of 25 mg/kg of body weight in sheep (n=6) B - zero-time concentration intercept of the elimination curve. β - hybrid rate constant for the elimination phase . t1/2 β - elimination phase half-life time. Vd (area) - volume of distribution. ClB – total body clearance. AUC 0-∞ -Area under the concentration vs. time curve .

15. Conclusion- The kinetic data for sheep 6 did not fit a one-compartment model. The data presented are for two compartment model.

16. REFERENCE- Brahmankar D.M., Jaiswal S.B., Biopharmaceutics and Pharmacokinetics – A Treatise, Published By Vallabh Prakashan, Delhi, 2 nd Edition, (2010), Pg. no-258-264. Kunudsen K.,Beckman M., Blomborg R.,Central nervous and cardio vascular effects of i.v. infusions of ropivacaine,bupivacaine and placebo in healthy volunteers.British Journal of Anaesthesia,Vol-3,(2015),Pg. no-245-320. Patel Chirag,Smita R.,Effect of i.v. infusion of dexmedetomidine on perio perative haemo haemodynamic changes and postoperative recovery : A study with entropy analysis,International Journal of Anaesthesia,Vol . 56,(2012), P g no-213-223 . Dimitrova D., Pharmacokinetics Of Dicloxacillin Sodium After Intravenous And Intramuscular Administration To Sheep, Trakia Journal Of Sciences, Vol. 2,(2004), Pg. no-14-18.