Multiple Dosage Oral Administration/ Dosage Regimen

Dosage regimen can be defined as the manner in which the drug is taken.

1. Dosage regimen BY NAUSHEEN FATHIMA M.PHARM (PHARMACEUTICS) TEEGALA KRISHNA REDDY COLLEGE OF PHARMACY 1

2. CONTENTS introduction to Dosage regimen approaches Parameters Drug accumulation Steady state during multiple dosing Maximum and minimum concentration during multiple dosing AVERAGE CONCENTRATION AND BODY CONTENT Loading dose Maintenance of Drug within the Therapeutic Range Monitoring drug therapy Conclusion references 2

3. INTRODUCTION Dosage regimen can be defined as the manner in which the drug is taken. A single dose may provide an effective treatment. But the duration of illness is longer than the therapeutic effect produced by a single dose. In such cases drugs are required to be taken on a repetitive basis over a period of time. 3

4. The multiple dosing achieves and maintains drug concentration in plasma or at the site of action that are both safe and effectively within the therapeutic window for the entire duration of therapy. 4

5. APPROACHES Empirical dosage regimen: D esigned by the physician based on empirical clinical data, personal experience and clinical observations. (not accurate ) Individualized dosage regimen : B ased on pharmacokinetics of the drug in individual patient. (most accurate) 5

6. 3. Dosage regimen on population averages : most often used. a. F ixed model: Calculated based on population average pharmacokinetic parameters. b. A daptive model : based on both population average pharmacokinetic parameters of drug and patient variables like weight, age ,body surface area. 6

7. The dose size: It is the quantity of the drug administered each time. PARAMETERS 7

8. Dose frequency : It is the time interval between doses. 8

9. DRUG ACCUMULATION Following the 1 st dose, if the 2 nd dose is given early enough so that not the entire 1 st dose is eliminated then the drug will start accumulating and we will get higher concentration with the 2 nd and 3 rd dose. R ac = 1/1- e -K   9

10. The suitable amount of dose and identical dosing interval leads to steady state at which the mass of drug administered or absorbed is equal to the mass of drug eliminated STEADY STATE DURING MULTIPLE DOSING 10

11. Maximum and minimum concentration during multiple dosing If n is the number of doses administered, the C max and C min obtained on multiple dosing after the nth dose is given as: C n,max ­ = C [ 1- / 1- ] C n,min = C [1- / 1- ] = c n,max The maximum and minimum concentrations of drug in plasma at steady-state are found by following equations: C ss,max = C / 1- C ss,min = C­ / 1- = c ss,max   11

12. Fraction of dose absorbed F, Maintenance dose X , 3. Clearance Cl t of the drug. 4. Dosing interval C ss,av = Fx / C l t = 1.44FX / v d = AUC (single dose) /   AVERAGE CONCENTRATION AND BODY CONTENT 12

13. Since X = V d C, the body content at steady-state is given as: X ss,av = 1.44FX t 1/2 / These averages values are not arithmetic mean of C ss,max and C ss,min since the plasma drug concentration declines exponentially.   13

14. Loading Dose A drug dose does not show therapeutic activity unless it reaches the desired steady state. It takes about 5 half lives to attain it and therefore time taken will be too long if the drug has a long half-life. Therapeutic effect can be reached immediately by administering a dose that gives the desired steady state instantaneously before the commencement of maintenance dose X0. Such an initial or first dose intended to be therapeutic is called as priming dose or loading dose. 14

15. Initial dose intended to be therapeutic is known as loading dose. X 0,l = C ss,av V d / F When V d is not known, loading dose may be calculated by the following equation: X 0,L / X = 1 / (1 - ) (1 - ­) The above equation applies when k a >>k e and during is distributed rapidly.   15

16. The ratio of loading dose to maintenance dose X 0,L /X is called as dose ratio. As a rule, when = t1/2 , dose ratio equals 2.0 > t1/2 , dose ratio is smaller than 2.0 < t1/2 , dose ratio is greater than 2.0.   16

17. Maintenance of Drug within the Therapeutic Range Depends upon- The therapeutic index of the drug. The half-life of the drug. Convenience of dosing. Certain generalization with regards to maintenance of drug within the therapeutic range can be stated – For a drug with a short half-life and narrow therapeutic index e.g. Heparin, dosing frequency has to essentially less than t 1/2 . 17

18. For a drug with short half-life and high therapeutic index, dosing frequency can be several times that of t 1/2 but the maintenance dose has to be larger so that the plasma concentration persists above the minimum inhibitory level. A drug with intermediate t 1/2 may be given at intervals t 1/2 if therapeutic index is low and those with high indices can be given at intervals between 1 to 3 half-lives. For drugs with very long half-lives e.g. Amlodipine, once daily dose is very convenient.   18

19. Monitoring drug therapy Management of drug therapy in individual patient often requires evaluation of response of the patient to recommended dosage regimen. Depending upon the drug and the disease to be treated, management of drug therapy in individual patient can be accomplished by: 1. Monitoring therapeutic effects- Therapeutic Monitoring 2. Monitoring pharmacological action – Pharmacodynamics M onitoring 3. Monitoring plasma drug concentration – P harmacokinetic Monitoring. 19

20. Conclusion Dosage regimen explains the interrelationship between the rate at which drug enters the body and the rate at which it leaves. It also explains how, in turn, this balance influences the concentration of drug in the plasma at any time. It is important for pharmaceutical sciences to come to terms with this problem and then overcome it by finding ways of maintaining therapeutic drug levels appropriate to a particular disease state. This can be achieved by the careful design of the appropriate drug delivery system. 20

21. references D.M. Brahmankar , Sunil.B.Jaiswal - Bio P harmaceutics A nd Pharmacokinetics- A treatise, pg.no: 368 – 376, 382 – 384. V.Venkateshwarlu - Bio P harmaceutics a nd P harmacokinetics, second edition, pg.no:311323. h ttp://pharmatechbd.blogspot.in/?search=dosage+regimen#uds-search-results h ttp://www.slideshare.net/vrushankshah/dosage-regimen?from_search=2 21

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