1) The document discusses one compartment intravenous infusion models and summarizes four research articles on this topic. 2) One compartment intravenous infusion models describe drug administration via constant intravenous infusion and the establishment of steady state plasma concentrations. The steady state concentration is directly proportional to the infusion rate and inversely proportional to drug clearance. 3) The research articles study intravenous infusions of local anesthetics, dexmedetomidine, and dicloxacillin in humans and sheep and analyze the pharmacokinetic parameters and effects.

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

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-
1. Iv bolus
2. Iv infusion
3. Extra vascular administration ,zero order
4. 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. Factors 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=R0÷CL
Css=Drug plasma conc. at steady state.
CL = Clearance
R0=Infusion rates

7. (The 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

12. 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-

13. 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

15.  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-

16. 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.

17. (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-

18. 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 .
t1/2β - elimination phase half-life time.
Vd(area) - volume of distribution.
ClB – total body clearance.
AUC 0-∞ -Area under the concentration vs. time curve.

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

20. REFERENCE-
 Brahmankar D.M., Jaiswal S.B., Biopharmaceutics and
Pharmacokinetics – A Treatise, Published By Vallabh Prakashan,
Delhi, 2nd 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
perioperative haemo haemodynamic changes and postoperative
recovery: A study with entropy analysis,International Journal of
Anaesthesia,Vol. 56,(2012),Pg 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.