Intravenous (IV) Infusion
• Intravenous drug solutions may be infused slowly through a vein into the plasma at a constant or zero-order rate.
• The main advantage are:
• IV infusion allows precise control of plasma drug concentrations.
• Fluctuations between maximum and minimum plasma drug concentrations can be controlled by IV infusion for drugs with narrow therapeutic window (eg, heparin).
• The IV infusion of drugs, such as antibiotics, may be given with IV fluids that include
electrolytes and nutrients.
• Furthermore, the duration of drug therapy may be maintained or terminated as needed
using IV infusion.
• One-compartment model – IV infusion
• Steady-state drug concentration and time needed to reach CSS
• Loading dose plus IV infusion
• Two-compartment model – IV infusion
• Loading dose for two-compartment Model
Biopharmaceutics And Pharmacokinetics
- Subject:- Biopharmaceutics And Pharmacokinetics
- Course:- B.pharm (pharmacy),
- Semester:- 6th sem , sem :- 6
Intravenous Infusion www.remixeducation.in Intravenous (IV) Infusion â€¢ Intravenous drug solutions may be infused slowly through a vein into the plasma at a constant or zero-order rate. â€¢ The main advantage are: ï�¶IV infusion allows precise control of plasma drug concentrations. ï�¶Fluctuations between maximum and minimum plasma drug concentrations can be controlled by IV infusion for drugs with narrow therapeutic window (eg, heparin). ï�¶The IV infusion of drugs, such as antibiotics, may be given with IV fluids that include electrolytes and nutrients. ï�¶Furthermore, the duration of drug therapy may be maintained or terminated as needed using IV infusion. www.remixeducation.in The plasma drug concentration-versus-time curve of a drug given by constant IV infusion is shown in the figure below. Because no drug was present in the body at zero time, drug level rises from zero drug concentration and gradually becomes constant when a plateau or steady-state drug concentration is â€¢ Plasma reached. At steady state, the rate of Level drug leaving the body is equal to the rate of drug (infusion rate) entering the body. Therefore, at steady-state, the rate of change in plasma drug concentration dCP/dt = 0. Time www.remixeducation.in One-compartment model â€“ IV infusion â€¢ For one compartment, pharmacokinetics of a drug by constant IV infusion follows zero-order input directly into the systemic blood circulation, however, the output rate will be first-order, i.e. first-order elimination rate. The change in the amount of drug in the body at any time (dDB/dt) during the infusion is the rate of input minus the rate of output. dD B ï€½ R inf ï€ kD B dt â€¢ Integration of above equation gives: CP ï€½ R inf ï€¨1 ï€ e ï€© ï€ kt VD k â€¢ At infinite time, t = âˆž, e-kt approaches zero, R inf R inf C ss ï€½ ï€½ VD k Cl www.remixeducation.in Steady-state drug concentration and time needed to reach CSS CSS = Rinf/VD.k If a drug is given as a continuous intravenous infusion, serum concentrations increase until a steady-state concentration (Css) is achieved. When the infusion is discontinued, serum concentrations decline in a straight line if the graph is plotted on semi-logarithmic axes. The elimination rate constant (k) can be computed using the following formula: slope =âˆ’k/2.303 www.remixeducation.in In clinical practice, the steady-state is considered to be reached after five half-lives. www.remixeducation.in If a drug is given at a more rapid infusion rate, a higher steady-state drug concentration is obtained but the time to reach steady-state is the same. www.remixeducation.in Loading dose plus IV infusion â€¢ The time required to obtain steady-state plasma levels by IV infusion will be long. It is possible to administer an intravenous loading dose to attain the desired drug concentration immediately and then attempt to maintain this concentration by a continuous infusion. â€¢ For a one-compartment drug, if the loading dose (DL) and infusion rate(Rinf) are calculated such that initial dose (C0) and CSS are the same and both DL and infusion are started concurrently, then steady state and CSS will be achieved immediately after the loading dose is administered. www.remixeducation.in www.remixeducation.in Two-compartment model â€“ IV infusion â€¢ Many drugs given by IV infusion follow two-compartment kinetics. For example, the respective distributions of theophylline and lidocaine in humans are described by the two-compartment open model. With two compartment model drugs, IV infusion requires a distribution and equilibration of the drug before a stable blood level is reached. During a constant IV infusion, drug in the tissue compartment is in distribution equilibrium with the plasma; thus, constant CSS levels also result in constant drug concentrations in the tissue; i.e., no net change in the amount of drug in the tissue occurs at steady state. www.remixeducation.in Loading dose for two-compartment Model â€¢ Drugs with long half-lives require a loading dose to more rapidly attain steady-state plasma drug levels. It is clinically desirable to achieve rapid therapeutic drug levels by using a loading dose. However, for drugs that follow the two-compartment pharmacokinetic model, the drug distributes slowly into extravascular tissues. Thus, drug equilibrium is not immediate. Plasma drug level after various loading doses and rates of infusion for a drug that follows a two-compartment model: a, no loading dose; b, loading dose = R/k (rapid infusion); c, loading dose = R/b (slow infusion); and d, loading dose = R/b (rapid infusion). www.remixeducation.in Thank you www.remixeducation.in