Bioavailability refers to the percentage of an administered drug dose that reaches systemic circulation in an unchanged form. It is calculated as the bioavailable dose divided by the administered dose. Absolute bioavailability compares bioavailability of a non-intravenous dose to an intravenous dose, while relative bioavailability compares bioavailability between different formulations of the same drug. Many factors can affect a drug's bioavailability including its physical properties, the dosage form, physiological factors like pH and transit time, and first-pass metabolism. Volume of distribution represents the hypothetical volume that the drug distributes into in the body and half-life is the time for a drug amount or concentration to reduce by half, which is affected by volume of distribution and clearance.

1. Bioavailability (F)
• The percentage of drug, contained in a drug
product, that enters the systemic circulation in
an unchanged form after administration of the
product.
F = Bioavailable dose
Administered dose

2. A typical time plasma curve

5. Absolute Bioavailability
• Compares the bioavailability of the active drug in systemic
circulation following non-intravenous administration with the same
drug following intravenous administration
 For drugs administered intravenously, bioavailability is 100%
 Determination of the best administration route
Fabsolute = (AUC)non-IV
(AUC)IV

6. Relative Bioavailability
• Compares the bioavailability of a formulation
(A) of a certain drug when compared with
another formulation (B) of the same drug,
usually an established standard
F relative = ( AUC) test formulation
(AUC) reference standard/established standard

7. Pharmacokinetic parameters
S.N. Parameters Unit Examples of drug
Paracetamol Chloroquine
1 Bioavailability (F)
(Fraction of drug
absorbed)
0-1
No unit
% 88±15 80
2 Volume of distribution Litres/Kg .95±.02 260
3 Half life Min or hr or
day
2±0.4 hrs 10-24 days
4 Peak conc. pg or ng or mcg
or mg per ml
20 mcg/ml 76 ng/ml
5 Peak time Min or hr or
day
0.3 to 1.3 hr 3 days
6 Clearance ml/min/kg 5 ml/min/kg 3.7 ml/min/kg
7 AUC ng hr/ml

8. • E.g.:
Drug products Dose (mg) AUC (mcg/ml/hr)
Oral tablet (a) 200 mg 89.5
Oral suspension(b) 200 mg 86.1
I.V. Bolus 50 mg 37.8
Relative bioavailability = [AUC]a = 89.5 = 1.04
[AUC]b 86.1
= 1.04 X 100 = 104 %
Absolute bioavailability = [AUC] po /Dose PO
[AUC]iv / Dose IV
=89.5/200 = .59
37.8/50
= 59%
Clearance = Dose = 200 = 2.234ml/min/kg
AUC 89.5

9. Factors affecting Bioavailability of a Drug
 Physical properties of a drug
 Physical state:
• Liquids > Solids
[ Solution > Suspension > Capsule > Tablet > Coated tablet ]
Crystalloids > Colloids
 Lipid or water solubility:
• Aqueous phase at absorption site
• Passage across Cell surface
 Dosage forms
 Particle size:
• Important for sparingly soluble drugs
• ↓ the size, ↑ the absorption, ↓ the dose
• Nano-crystalline formulations of Saquinavir
• If ↓ absorption needed (local action on GIT), ↑ the size

10.  Physiological factors
 Ionization:
• Unionized form penetrates the GI mucosal lining quickly
 pH of the fluid:
• Weakly acidic drugs: Aspirin, Barbiturates→ Stomach, duodenum
• Weakly basic drugs: Pethidine, Ephedrine→ Small intestine
• Strongly acidic / basic drugs: highly ionized & poorly absorbed
 GI transit time
 Prolonged gastric emptying:
• Delays absorption due to stasis
(e.g. with anticholinergics / Diabetic neuropathy)
 Increased peristaltic activity:
(e.g. Metoclopramide→ speeds up the absorption of analgesics)
 Excessive peristaltic activity (as in Diarrhoea) impairs absorption
 Fed state:
• impairs progress of drug to intestine→ ↓ absorption (Indinavir)
• ↑ splanchnic blood flow→ ↑ absorption (Propranolol)

11. First pass metabolism:
• Gut wall (e.g. Isoprenaline)
• Liver (e.g. Opoids, ß-blockers, Nitrates)
Presence of other agents:
• Vitamin C ↑ Iron absorption, Phytates retard it
• Calcium ↓ absorption of Tetracyclines
Disease states:
• Malabsorption, Achlorhydria, Cirrhosis, Biliary
obstruction can hamper absorption
Entero-hepatic cycling:
• Increases bioavailability (e.g. Morphine, OC pills)

12. Volume of distribution
• Volume of distribution is defined as the hypothetical
volume of body fluid into which a drug is dissolved or
distributed. It is called apparent volume because all
parts of the body equilibrated with the drug do not
have equal concentration.
Apparent volume of distribution = amount of drug in the body
plasma drug concentration
Unit of Vd = litres /Kg body weight

13. Plasma concentration-time curves following intravenous administration of a drug (500 mg) to
a 70-kg patient.

14. Factors affecting volume of
distribution
• Tissue permeability of the drug
a. Physiochemical properties of the drug like molecular
size, pKa and O/W partition coefficient
b. Physiological barriars to diffusion of drugs.
• Organ / tissue size and perfusion rate
• Binding of drugs to tissue components
(blood components and extravascular tissue proteins)
• Miscellaneous factors
(Age, pregnancy, obesity, diet, Medical conditions, and
drug interactions..)

15. Half life (t1/2)
• It is defined as the time taken for the amount of drug
in the body as well as plasma concentration to
decline by one-half or 50% its initial value.
t1/2= 0.693 x Vd
CL

17. • 1 t1/2 – 50% drug is eliminated
• 2 t1/2– 75% (50 + 25) drug is eliminated
• 3 t1/2– 87.5% (75 + 12.5) drug is eliminated
• 4 t1/2– 93.75% (87.5 + 6.25) drug is eliminated
• 5 t1/2– 96.875% (93.75 + 3.125) drug is
eliminated
• It takes about 4-5 half life to reach clinical steady
state

18. Loading dose
• Initial or first dose intended to be therapeutic
is called as loading dose
Loading dose = Vd x target Conc. (mg/L)(Css)
bioavailability
Dosing rate (maintenance dose) (mg/time) = CL x target Conc. (mg/L)
bioavailability
Target Conc.(Cpss) = Dose rate
CL
Revised drug rate = Previous dosing rate X target Cpss
measured Cpss

20. Therapeutic window
• Useful range of concentration over which a drug is therapeutically beneficial.
Therapeutic window may vary from patient to patient
• Drugs with narrow therapeutic windows require smaller and more frequent doses
or a different method of administration
• Drugs with slow elimination rates may rapidly accumulate to toxic levels….can
choose to give one large initial dose, following only with small doses