415 PHT Plasma Level – Time Curve Dr. Ahmed Alalaiwe a.alalaiwe@psau.edu.sa Office: 13A-1 Office Hours: Wed 01-03 pm 1437 - 2016

Objectives By the end of this lecture, you will be able to: Understand the concept of drug response relationships Define the major pharmacokinetic parameters related to plasma level curve Differentiate the plasma level curve profiles based on their expression

Drug Response Relationships Time Response Dose Response

Time Response Relationships Maximal (Peak) Effect Effect/ Response Latency Duration of Response Time

Time Response Relationships Effect/ Response Time

Dose Response Relationships Potency Absolute amount of drug required to produce an effect More potent drug is the one that requires lower dose to cause same effect. Efficacy is the maximal response produced by the drug.

Dose Response Relationships B Effect Dose A Therapeutic Effect Which drug has the lower threshold dose? Which has the greater maximum effect?

Plasma Level – Time Curve The plasma level–time curve is generated by obtaining the drug concentration in plasma samples taken at various time intervals after a drug product is administered. In general, serum or plasma is most commonly used for drug measurement Generalized plasma level–time curve after oral administration of a drug.

Plasma Level – Time Curve Generalized plasma level–time curve after oral administration of a drug

Plasma Level – Time Curve As the drug reaches the general (systemic) circulation, plasma drug concentrations will rise up to a maximum. Usually, absorption of a drug is more rapid than elimination As the drug is being absorbed into the systemic circulation, the drug is distributed to all the tissues in the body and is also simultaneously being eliminated Elimination of a drug can proceed by excretion, biotransformation, or a combination of both

Plasma Level – Time Curve The MEC (minimum effective concentration) reflects the minimum concentration of drug needed at the receptors to produce the desired pharmacologic effect The MTC (minimum toxic concentration) represents the drug concentration needed to just barely produce a toxic effect

Plasma Level – Time Curve The onset time corresponds to the time required for the drug to reach the MEC The intensity of the pharmacologic effect is proportional to the number of drug receptors occupied, which is reflected in the observation that higher plasma drug concentrations produce a greater pharmacologic response, up to a maximum The duration of drug action is the difference between the onset time and the time for the drug to decline back to the MEC

Plasma Level – Time Curve The time of peak plasma level is the time of maximum drug concentration in the plasma and is a rough marker of average rate of drug absorption The peak plasma level or maximum drug concentration is related to the dose, the rate constant for absorption, and the elimination constant of the drug The AUC is related to the amount of drug absorbed systemically Plasma level–time curve showing peak time and concentration. The shaded portion represents the AUC (area under the curve)

Plasma Level – Time Curve

Important parameters in bioavailability studies Time to Peak (Tmax): the time after admin that it takes for the drug to reach Cmax. This is an indication of the rate of absorption. Max. conc. Attained (Cmax): assesses whether concentration is in therapeutic range Area Under the Curve (AUC): Total drug absorption, reflects changes in distribution, metabolism & excretion Onset of Action: The time required to reach the MEC. following drug admin. Duration of Action: The time period in which the plasma conc. Exceeds MEC. Intensity: the difference in the MEC and Cmax.

Important parameters in bioavailability studies Absorption rate conctant (ka): assesses the rate of drug absorption from a formulation Minimum Effective Concentration (MEC): minimum plasma conc. that must be reached before achieving therapeutic effect. Maximum Safe Concentration (MSC): the conc. above which toxic effects are seen. Minimum Toxic Concentration (MTC): The minimum concentration at which the toxic effect of the drug is seen. Therapeutic Range: Plasma conc. range bet. MEC and MSC.

Blood Concentration-Time Profiles Minimum effective dose (MEC) Smallest concentration of the drug that is sufficient to cause an effect. Minimum Toxic Concentration (MTC): Smallest concentration beyond which the there are undesirable or toxic effect. Therapeutic window Range between MEC and MTC. Duration of action Time the drug should above the MEC.

Blood Concentration-Time Profiles

Blood Concentration-Time Profiles

Concentration vs Time Graph

Bioavailability - AUC AUC – area under the curve F – bioavailability AUC p.o. F = ------------ x 100% AUC i.v.

Bioavailability - AUC

Bioavailability - AUC