This document discusses pharmacokinetic drug interactions, including factors that influence them, mechanisms, and classifications. It describes several important interaction types like absorption interactions caused by complexation/adsorption or changes in GI pH. Distribution interactions can involve protein binding alterations, while metabolism interactions may be due to enzyme induction/inhibition. Excretion interactions can change active tubular secretion or urine pH. The effect of protein binding is explained using equations for volume of distribution and hepatic clearance. Cytochrome P450 inhibitors can increase drug bioavailability by inhibiting hepatic metabolism. In conclusion, recognizing interaction principles and vigilance when changing drugs can help identify harmful interactions.

1. PHARMACOKINETIC DRUG INTERACTIONS
Presented by
Sujitha mary
Mpharm
St joseph college of pharmacy
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2. CONTENTS
• Introduction
• Factors affecting drug interactions
• Mechanism of drug interaction
• Classification of pharmacokinetic drug interactions
• Conclusion
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3. Introduction
• Drug interactions occur when the pharmacological activity
of a drug is altered by the concomitant use of another drug
or by the presence of some other substance.
• The drug whose activity is affected by such an interaction
is the object drug and the agent which precipitates such an
interaction is referred to as the precipitant.
• A drug interaction generally refers to a modification of the
expected drug response in the patient as a result of
another drug or substance.
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4. • Drug interactions may include drug-drug interaction,
food-drug interaction, chemical-drug interactions.
• Drug interaction may cause an alteration in the
pharmacokinetics of drug due to an interaction in drug
absorption, distribution or elimination.
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5. FACTORS AFFECTING DRUG INTERACTIONS
1.Multiple drug therapy
2.Multiple prescribers
3.Multiple pharmacological effects of drug
4.Multiple diseases/ predisposing illness
5.Poor patient compliance
6.Advancing age of patients
7.Drug-related factors
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6. MECHANISMS OF DRUG INTERACTIONS
• Pharmaceutical interaction:
Also called as incompatibility, it’s a physicochemical interaction that
occurs when drugs are mixed in i.v infusions causing precipitation or
Inactivation of active principles. For eg. Ampicillin, chlorpromazine
and barbiturates interact with dextran in solutions and are broken
down or form chemical complexes.
• Pharmacokinetic interactions:
These interactions are those in which the absorption, distribution,
metabolism and/or excretion of the object drug are altered by the
precipitant and hence such interactions are aka ADME
interactions. The resultant effect is altered plasma conc. of the
object drug.
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7. CLASSIFICATION OF PHARMACOKINETIC INTERACTIONS
I. Absorption interactions: are those where the absorption of the
object drug is altered. The net effect of such an interaction is:
– Faster or slower drug absorption
– More, or, less complete drug absorption.
Major mechanisms of absorption interactions are:
– Complexation and adsorption
– Alteration in GI pH
– Alteration in gut motility
– Inhibition of GI enzymes
– Alteration of GI microflora
– Malabsorption syndrome
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8. II. Distribution interactions: are those where the distribution pattern of
the object is altered. The major mechanism for distribution
interaction is alteration in protein-drug binding.
III. Metabolism interactions: are those where the metabolism of the
object drug is altered. Mechanisms of metabolism interactions
include-
– Enzyme induction: increased rate of metabolism
– Enzyme inhibition: decreased rate of metabolism.
IV.Excretion interactions: are those where the excretion pattern of the
object drug is altered. Major mechanisms of excretion interactions
are-
– Alteration in renal flow
– Alteration of urine pH
– Competition for active secretion
– Forced diuresis
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9. IMPORTANT PHARMACOKINETIC INTERACTIONS
• ABSORPTION INTERACTIONS:
1. Complexation and adsorption:
Tetracyclines, fluoroquinolones like ciprofloxacin, penicillamine react with
antacids, food and mineral supplements containing Al, Mg, Fe, Zn, Bi, and Ca ions
which would lead to formation of poorly soluble and unabsorbable complex with
such heavy metal ions.
2. Alteration of GI pH:
Sulphonamides, aspirin react with antacids that leads to enhanced dissolution
and absorption rate.
3. Alteration of gut motility:
Levodopa, lithium carbonate reacts with anticholinergics which results in
delayed gastric emptying; decreased rate of absorption.
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10. 4.Malabsorption syndrome:
Vitamin A, B12, digoxin reacts with neomycin which results in inhibition of absorption
due to malabsorption caused by neomycin.
DISTRIBUTION INTERACTIONS
Competitive displacement interactions:
Anticoagulants are displaced by phenyl butazone, chloral hydrate, salicylates which
results in increased clotting time hence leading to increased risk of haemorrhage.
METABOLISM INTERACTIONS
Enzyme induction:
Corticosteroids, oral contraceptives, coumarins react with barbiturates which results in
decreased plasma levels and decreased efficacy of object drugs.
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11. EXCRETION INTERACTIONS
1.Changes in active tubular secretion:
Procainamide, ranitidine reacts with cimetidine which
increases plasma levels of basic object drugs; risk of toxicity.
2.Changes in urine pH:
Amphetamine, tetracycline, quinidine react with antacids,
thiazides, acetazolamide which results in increased passive
reabsorption of basic drugs, hence increased risk of toxicity.
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12. THE EFFECT OF PROTEIN BINDING INTERACTIONS
Changes in volume of distribution
The general equation that expresses the apparent volume of
distribution at steady state (Vss) as a function of its contributing
parameters is:
Vss = 7.5+ 7.5(fup) Vincell (fup/ fut)
where fup is the fraction drug unbound in the plasma;
fut is fraction drug unbound in the tissues;
And Vincell is the intracellular fluid volume available for drug
distribution.
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13. Changes in hepatic clearance
The general equation expressing hepatic clearance as a function of its
contributing parameters :
ClH = QH fup Clint /QH þ fup Clint
where ClH is hepatic clearance from plasma;
QH is plasma flow to the liver;
fup is the fraction drug unbound in the plasma;
and Clint is intrinsic plasma clearance of unbound drug.
The product fup Clint equals Clint, the intrinsic clearance of bound plus
free drug
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14. The effect of tissue-binding interactions
The apparent volume of distribution at steady state is given by
the general equation:
Vss = 7.5 + 7.5 (fup) + Vincell (fup /fut)
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15. Cytochrome P450-based drug interactions
• Grapefruit juice and azole antifungal drugs such as ketoconazole
can inhibit the elimination of the hydroxymethylglutaryl-coenzyme
A (HMG-CoA) reductase inhibitors lovastatin and simvastatin.
• After oral dosing, these two drugs are normally extracted rapidly
by the liver (first-pass effect).
• Therefore, their bioavailability can be greatly amplified under
conditions that inhibit their metabolism in the liver, leading to
pronounced physiological effects.
• As the normal fraction of drug extracted by the liver becomes less,
the amplification of bioavailability caused by metabolic inhibition
will also become less pronounced.
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16. CONCLUSION
• Most potential drug interactions can be recognised by applying principles of clinical pharmacology
and good clinical care.
• Increased vigilance by clinicians at the time of changing drugs improves the chance of identifying
unwanted drug interactions before they cause significant harm.
• Knowing a few drugs well and making judicious use of available information is more effective for
managing drug interactions than relying solely on electronic decision support.
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17. REFERENCES
1.Leon Shargel, Susanna Wu-pong, Andrew Yu, Applied
Biopharmaceutics and Pharmacokinetics, McGraw-Hill
companies, Singapore, 2013. p.590-594.
2.Sunil S. Jambhedkar, Philip J. Breen, Basic Pharmacokinetics,
Pharmaceutical press, London, 2009, p. 319-328.
3.D.M. Brahmankar, Sunil B. Jaiswal, Biopharmaceutics and
Pharmacokinetics, Vallabh Prakashan, India, 2016, p. 226-235.
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