This document discusses approaches for designing drug dosage regimens, including individualized regimens based on a patient's pharmacokinetic parameters, population-based regimens that use average parameters, and empirical regimens based on clinical experience. It also describes using nomograms and tabulations to simplify calculations and software programs that can improve accuracy. The key factors considered in regimen design are the drug's route of administration, dose, dosage interval, and any complications.

1. (Clinical pharmacokinetics)
Presented to: Dr. Saeed ur Rashid
Presented by: Muniba Iqbal
Roll.no: PPCS20E003
M.Phil pharmacy practice (2020-2022)
College of pharmacy, UOS

2. Contents
 Introduction
 Factors to consider in Design of Drug Dosage
Regimens
 Approaches used to design a dosage regimen
 Nomograms and tabulations in designing dosage
regimens
 Software progarms

3. Introduction
 It is the selection of drug dosage, route, and frequency of
administration in an informed manner to achieve therapeutic
objectives.
 Administration of drugs usually involves risk of untoward effects
 Dosage regimen should be selected which will maximize safety
 Variability among patients in pharmacodynamic response
demands individualized dosing to assure maximum efficacy.[1]

4. Factors to consider in Design of
Drug Dosage Regimens
1. Route of Administration:
 Drug absorption characteristics
 Presence of presystemic elimination
 Accumulation of drug at absorption site, e.g. intramuscular depots
 Need for immediate onset of action
 Ease of administration
 Half-life
 Patient acceptance of route and dosage form.[1]

5. 2. Dose:
 Volume of distribution
 Therapeutic index
 Documented nonlinearity of pharmacokinetics
 Cost of medication
 Half-life: tapering of dose may not be necessary for some drugs with
long t1/2
 Availability of treatment for overdose
 Existence of a therapeutic or toxic concentration range. [1]

6. 3. Dosage interval:
Half-life
Therapeutic index
Body clearance
Side effects which may require special administration
times, e.g. bedtime to avoid sedation. [1]

7. 4. Complications:
 Analytical methodology and reliability in monitoring Cp
 Active metabolites
 Changing pathophysiology
 Drug interactions
 Auto or exogenous enzyme induction
 Development of pharmacodynamic tolerance
 Side effects not dose or concentration related
 Need for baseline con. data with recent history of drug use. [1]

8. Approaches used to design a
dosage regimen
I. Individualized dosage regimen
II. Dosage regimen based on population average
III. Dosage regimen based on partial pharmacokinetic
parameters
IV. Empirical dosage regimen

9. 1. Individualized Dosage Regimen
 Most accurate approach
 Dose calculated based on the pharmacokinetics of the drug in
the individual patient
 Not feasible for calculation of the initial dose
 Readjustment of the dose is quite possible
 Record the patient’s age and weight and calculate the individual
dose based on creatinine clearance and lean body mass. [2]

10. 2. Dosage Regimens based on
Population Averages
 Dosage regimen is calculated based on average pharmacokinetic parameters
 Based on clinical studies published in literature.
 There are two approaches followed
Fixed model
Adaptive model
Fixed Model:
 Population average pharmacokinetic parameters may be used directly, without
any alteration.
 Usual dosage suggested by the literature
 Small adjustment of the dosage based on patient’s weight/ age.

11.  Ka, F, Vd, k are assumed remain constant
 Multiple dosage equations based on the principle of superposition are
used to evaluate the dose.
Adaptive Model:
 Adapt or modify dosage regimen according to the need of the patient
 Uses patient variable such as weight, age, gender, body surface area,
and known patient’s pathophysiology such as, renal disease
 Allow for continuously adaptive change with time. [2]

12. 3. Regimen based on Partial
Pharmacokinetic Parameters
 For drugs with unknown pharmacokinetic profile
 Pharmacokineticist needs to make some assumptions
 These assumptions will depend on the safety, efficacy, and
therapeutic range of the drug
 Uses average patient population characteristics and only a few
serum / plasma concentration from the patient
 Therapeutic drug monitoring have increased with the increased
availability of computerized data bases and statistical tools.[2]

13. 4. Empirical Dosage Regimens:
 In many cases, physician selects a dosage regimen of
the patient without using any pharmacokinetic
variables
 The physician makes the decision based on empirical
clinical data, personal experience and clinical
observations. [2]

14. Nomograms and tabulations in
designing dosage regimens
 A nomogram typically has three scales
 Two scales represent known values & one scale is where the result is read off
 The known scales are placed on the outside; i.e. the result scale is in the center
 Each known value of the calculation is marked on the outer scales and a line is
drawn between each mark
 Where the line and the inside scale intersects is the result
 Examples include, height – BMI – weight, total clearance – maintenance dose –
lean body weight, etc.[3]

15. Nomograms and tabulations in
designing dosage regimens
 keep the dosage regimen calculation simple
 Some nomograms make use of certain physiologic
parameters, such as serum creatinine concentration
 For many marketed drugs, the manufacturer provides
tabulated general guidelines for use in establishing a
dosage regimen for patients, including loading and
maintenance doses. [3]

16. Examples of drugs for which nomograms are being
used for designing dosage regimen[3]:
 Digoxin
 Warfarin
 Heparin
 Vancomycin
 Phenytoin
 Clozapine

17. Software programs
 Clinical pharmacokinetic software programs are
available for dosage regimen calculations
 Improve the accuracy
 Make calculation easier
 Maintaining proper documentation
 However, these softwares should not replace good
clinical judgment
 Example: Model-informed precision dosing (MIPD),
APIS. [4]

18. References
 Shargel, L., Andrew, B.C. and Wu-Pong, S., 1999. Applied
biopharmaceutics & pharmacokinetics (pp. 692-694).
 Thompson, G.A., 1992. Dosage regimen design: a
pharmacokinetic approach. The Journal of Clinical
Pharmacology, 32(3), pp.210-214.
 Williams, R.L., 1992. Dosage regimen design:
pharmacodynamic considerations. Journal of clinical
pharmacology, 32(7), p.597.
 Iliadis, A., Brown, A.C. and Huggins, M.L., 1992. APIS: a
software for model identification, simulation and dosage
regimen calculations in clinical and experimental
pharmacokinetics. Computer methods and programs in
biomedicine, 38(4), pp.227-239.