multiple dosage oral administration/ dosage regimen
TRANSCRIPT
CONTENTSINTRODUCTION 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
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.
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.
APPROACHES
1.Empirical dosage regimen: Designed by the physician based on empirical clinical data, personal experience and clinical observations. (not accurate)
2.Individualized dosage regimen: Based on pharmacokinetics of the drug in individual patient. (most accurate)
3. Dosage regimen on population averages : most often used.
a. Fixed model: Calculated based on population average pharmacokinetic parameters.
b. Adaptive model : based on both population average pharmacokinetic parameters of drug and patient variables like weight, age ,body surface area.
DRUG ACCUMULATION
Following the 1st dose, if the 2nd dose is given early enough so that not the entire 1st dose is eliminated then the drug will start accumulating and we will get higher concentration with the 2nd and 3rd dose.
Rac = 1/1- e-K
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
MAXIMUM AND MINIMUM CONCENTRATION DURING MULTIPLE
DOSINGIf n is the number of doses administered, the Cmax and
Cmin obtained on multiple dosing after the nth dose is given as:
Cn,max = C0 [ 1- / 1- ]
Cn,min = C0 [1-/ 1-] = cn,max
The maximum and minimum concentrations of drug in plasma at steady-state are found by following equations:
Css,max = C0 / 1-
Css,min = C 0 / 1- = css,max
1. Fraction of dose absorbed F, 2. Maintenance dose X0,
3. Clearance Clt of the drug.4. Dosing interval
Css,av = Fx0 / Clt
= 1.44FX0 / vd = AUC (single dose) /
•
AVERAGE CONCENTRATION AND BODY CONTENT
Since X = Vd C, the body content at steady-state is given as:
Xss,av = 1.44FX0 t1/2 / These averages values are not
arithmetic mean of Css,max and Css,min since the plasma drug concentration declines exponentially.
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.
Initial dose intended to be therapeutic is known as loading dose.
X0,l = Css,av Vd / F
When Vd is not known, loading dose may be calculated by the following equation:
X0,L / X0 = 1 / (1 - ) (1 - )
The above equation applies when ka>>ke and during is distributed rapidly.
• The ratio of loading dose to maintenance dose X0,L/X0 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.
MAINTENANCE OF DRUG WITHIN THE THERAPEUTIC
RANGEDepends 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 t1/2.
• For a drug with short half-life and high therapeutic index, dosing frequency can be several times that of t1/2 but the maintenance dose has to be larger so that the plasma concentration persists above the minimum inhibitory level.• A drug with intermediate t1/2 may be given at
intervals t1/2 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.
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 Monitoring 3. Monitoring plasma drug concentration – Pharmacokinetic Monitoring.
CONCLUSIONDosage 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
REFERENCES• D.M. Brahmankar, Sunil.B.Jaiswal- Bio
Pharmaceutics And Pharmacokinetics- A treatise, pg.no: 368 – 376, 382 – 384. • V.Venkateshwarlu- Bio Pharmaceutics and
Pharmacokinetics, second edition, pg.no:311323.• http://pharmatechbd.blogspot.in/?
search=dosage+regimen#uds-search-results• http://www.slideshare.net/vrushankshah/
dosage-regimen?from_search=221