Transcript Bioavailability Dr. Basavaraj K. Nanjwade M. Pharm., Ph. D Department of Pharmaceutics Faculty of Pharmacy Omer Al-Mukhtar University Tobruk, Libya. E-mail: [email protected] 2014/03/15 Faculty of Pharmacy, Omer Al-Mukhtar University, Tobruk,

Bioavailability
Dr. Basavaraj K. Nanjwade
M. Pharm., Ph. D
Department of Pharmaceutics
Faculty of Pharmacy
Omer Al-Mukhtar University
Tobruk, Libya.
E-mail: [email protected]
2014/03/15
Faculty of Pharmacy, Omer Al-Mukhtar University,
Tobruk, Libya.
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CONTENTS
1. Concept and terminology.
2. Methods of assessing bioavailability.
3. Evaluation and design of a single dose
bioequivalency study.
4. Determination
of
bioavailability
and
bioequivalency in multiple dose regimen.
5. References.
2014/03/15
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Tobruk, Libya.
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What is Bioavailability
• Bioavailability, Indicates measurement of the
rate and extent (amount) of therapeutically
active drug that reaches the systemic
circulation and is available at the site of
action.
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Tobruk, Libya.
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Concept of Bioavailability
• Rate and extent at which therapeutically active drug
reaches systemic circulation.
• The fraction of administered dose that reaches the
systemic circulation in contrast to that stated on
label.
• Rate & extent of absorption of unchanged drug from
its dosage form.
• A measure relative to some standard of rate &
amount of drug, which reaches the systemic
circulation unchanged following the administration
of dosage form.
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Faculty of Pharmacy, Omer Al-Mukhtar University,
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Why bioavailability studies
• FDA requires that the drug product is safe and
effective.
• Measure of bioavailability: AUC/dose.
• Absolute availability: Absolute availability for drugs
with approved NDA, bioavailability studies are
required for new drug formulations-bioequivalence to
the reference formulation.
• Relative availability: Relative availability for drugs
without full NDA, bioequivalence to the reference drug
in the standard formulation.
• For determining safety and efficacy of drug product.
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Types of Bioavailability
 Absolute Bioavailability :If the systemic availability of a drug administered
orally is determined by doing its comparison with I.V.
administration, it is known as absolute bioavailability.
AUC extravascular Dose int ravenous
F

AUC int ravenous Dose extravascular
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Types of Bioavailability
 Relative Bioavailability :If the systemic availability of a drug
administered orally is determined by doing its
comparison with that of an oral standard of
the same drug, it is known as a relative
bioavailability.
AUC extravascular1 Dose extravascular 2
Frel 

AUC extravascular 2 Dose extravascular1
2014/03/15
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University, Tobruk, Libya.
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Types of Bioavailability
 Range of Bioavailability – 0 to 1.
 It is usually expressed as percentages (%).
 An absolute bioavailability of 1 (or 100%) indicates
complete absorption.
 Relative bioavailability of 1 (or 100%) implies that the
bioavailability of drug from both the dosage forms is
the same but does not indicate the completeness of
the systemic drug absorption.
2014/03/15
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Tobruk, Libya.
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Types of Bioavailability
 Bioavailability of drug from dosage form
depends upon following.




Route of administration
Patient related factors
Physicochemical properties of the drug
Characteristics of the dosage form
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Bioavailability
• The influence of route of administration on
drug’s bioavailability is generally in the
following order
Parenteral > Oral > Rectal > Topical
• Most drugs are administered orally, for reason
of stability and convenience.
• The dose available to patient – Bioavailable
dose.
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Tobruk, Libya.
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Plasma concentration
Bioavailability
i.v. route
oral route
Time (hours)
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Methods of assessing
bioavailability
• Pharmacokinetic methods ( indirect )
1. Blood analysis
2. Urinary excretion data
• Pharmacodynamic methods ( direct )
1. Acute pharmacological response
2. Therapeutic response
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Pharmacokinetic methods
( indirect )
1. Blood analysis
• Plasma level time studies or The plasma
concentration – time curve or blood level curve.
• A direct relationship exists concentration of drug at
the site of action & concentration of drug in the
plasma.
• Serial blood samples are taken after drug
administration & analyzed for drug concentration.
• A typical blood level curve obtained after oral
administration of drug.
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Pharmacokinetic methods
( indirect )
2. Urinary excretion data
• The method of determination bioavailability
provided that the active ingredient is excreted
unchanged in the significant quantity of urine.
• The cumulative amount of active drug excreted in
urine is directly proportional to extent of systemic
drug absorption.
• The rate of drug excretion is directly proportional to
rate of systemic drug absorption.
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Pharmacodynamic methods
( direct )
1. Acute pharmacological response
• Bioavailability can be determined from the acute
pharmacologic effect – time curve as well as from
dose response graph.
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Pharmacodynamic methods
( direct )
2. Therapeutic response
• This method is based on the observing the clinical
response to a drug formulation given to a patients
suffering from disease for which it is intended to be
used.
Eg. Anti inflammatory drugs, the reduction in the
inflammation is determined.
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Pharmacokinetic and
Pharmacodynamic Parameters
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Parameters determined
Pharmacokinetic parameters
• Peak Plasma Concentration (Cmax)
• Time of Peak concentration (tmax).
• Area Under Curve (AUC)
Pharmacodynamics parameters
• Minimum Effective Concentration (MEC) / Minimum
Inhibitory Concentration (MIC).
• Maximum Safe Concentration (MSC) / Maximum Safe Dose
(MSD).
• Duration of action
• Onset of action.
• Intensity of action.
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AUC or Extent of absorption
can be measured by 3 methods
1.Planimeter
Instrument for mechanically measuring the area
2. Cut & weigh method
AUC is cut & weighed on analytical balance. The
weight obtained is converted to proper unit by
dividing it by the wt of a unit area of same paper.
3. Trapezoidal method
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AUC or Extent of absorption
can be measured by 3 methods
3. Trapezoidal method
AUC = ½ ( C1 + C2) (t2 – t1) + ½ (C2 + C3) (t3 – t2) +…….
½ (C n-1 + C n ) (tn – tn-1 )
C = Concentration
t = time
subscript= sample number
AUC = Area Under Curve
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Tobruk, Libya.
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Methods of assessing
bioavailability
• AUC-Area under curve
• Cmax - Maximum concentration
• Tmax -Time to maximum concentration
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Tobruk, Libya.
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Bioequivalence
- Bioequivalence means pharmaceutical equivalents or
pharmaceutical alternatives whose rate and extent of
absorption do not show a significant difference when
administered at the same molar dose of the
therapeutic moiety under similar experimental
conditions.
- Bioequivalence studies are usually performed to
compare the rate and/or extent of absorption of a
new drug product or a generic equivalent with that
of a recognized standard.
2014/03/15
Faculty of Pharmacy, Omer Al-Mukhtar University,
Tobruk, Libya.
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Evaluation and design of a single
dose bioequivalency study
Dosage forms that are to be evaluated only for
bioequivalence purpose.
Dosage forms meant for a single dose
administration for a therapeutic benefit such
as analgesic for relief of headache.
2014/03/15
Faculty of Pharmacy, Omer Al-Mukhtar University,
Tobruk, Libya.
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Evaluation and design of a single
dose bioequivalency study
2014/03/15
Faculty of Pharmacy, Omer Al-Mukhtar University,
Tobruk, Libya.
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Determination of bioavailability and
bioequivalency in multiple dose regimen
Dosage forms designed to achieve special
release profiles. e.g. time-release products,
enteric-coated preparations.
Drugs undergoing first pass metabolism.
Special dosage regimens such as loading dose.
2014/03/15
Faculty of Pharmacy, Omer Al-Mukhtar University,
Tobruk, Libya.
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Determination of bioavailability and
bioequivalency in multiple dose regimen
Dosage forms designed to achieve special
release profiles. e.g. time-release products,
enteric-coated preparations.
Drugs undergoing first pass metabolism.
Special dosage regimens such as loading dose.
2014/03/15
Faculty of Pharmacy, Omer Al-Mukhtar University,
Tobruk, Libya.
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Bioavailability and Bioequivalence
Two dosage forms are
bioequivalent:
2014/03/15
Two dosage forms are
not bioequivalent:
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Tobruk, Libya.
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References
• “Biopharmaceutics & Pharmacokinetics”, D. M.
Brahmankar & Sunil B. Jaiswal, Vallabh Prakashan.
• “Text book of Biopharmaceutics & pharmacokinetics”,
Dr. Shobharani R. Hiramath.
• “Applied Biopharmaceutics & pharmacokinetics”, Leon
Shargel & Andrew B.C.
• www.google.com
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Tobruk, Libya.
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THANK YOU
E-mail: [email protected]
2014/03/15
Faculty of Pharmacy, Omer Al-Mukhtar University,
Tobruk, Libya.
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