Biopharma Answer Key ( 2 marks ) created by

Nimish Shityalkar

1. Characteristics of passive diffusion of drugs:

- It is the most common route of drug absorption.

- It occurs along the concentration gradient.
- It does not require energy or carrier proteins.
- It is influenced by factors like lipid solubility, molecular size, and pH.

2. Hepatic first-pass effect:

- It refers to the rapid metabolism or degradation of a drug by the liver before it reaches
systemic circulation.
- It can significantly reduce the bioavailability of orally administered drugs.

3. Non-per oral extravascular routes of drug administration:

- Intravenous (IV) injection
- Intramuscular (IM) injection
- Subcutaneous (SC) injection
- Transdermal patches
- Inhalation
- Intranasal administration

4. Factors to be considered in oral mucosal drug delivery:

- Permeability of the oral mucosa
- pH of the drug formulation
- Drug concentration
- Contact time with the mucosa
- Presence of permeation enhancers

5. Steps involved in oral drug absorption from solid dosage forms:

- Disintegration of the tablet/capsule
- Drug dissolution in the gastrointestinal fluid
- Drug diffusion across the intestinal membrane
- Drug transport to the systemic circulation

6. Gastric emptying:
- It is the process by which the stomach releases its contents into the small intestine
for further digestion and absorption.
- Rapid gastric emptying is advisable when immediate drug action is desired.

7. Factors affecting gastric emptying:

- Food composition and volume
- Physical activity
- Stress and emotional state
- Medications and diseases
- Gastrointestinal motility disorders
8. Polymorphism: The ability of a substance to exist in multiple crystal forms.
Pseudopolymorphism: When a substance appears to have different crystal forms but
is actually due to solvation or non-crystalline forms.

9. Dissolution: The process in which a solid drug dissolves in a liquid to form a solution.
Theories of drug dissolution: Noyes-Whitney theory, Diffusion layer model, Film theory.

10. Modified Noyes-Whitney's equation: dM/dt = (D * A * (Cs - C))/h

The concentration gradient (Cs - C) affects the dissolution rate of a drug.

11. Sink condition in dissolution testing: When the concentration of the drug in the
dissolution medium is much lower than its solubility, ensuring that the drug dissolves
freely.
It can be achieved by using a large volume of dissolution medium.

12. Rate-determining step: The slowest step in a process that limits the overall rate of
that process.
Two major rate-determining steps in absorption of orally administered solid dosage
forms: disintegration and dissolution.

13. Bioavailability: The proportion of a drug that reaches systemic circulation and is
available to produce a pharmacological effect.
Orally administered dosage forms in order of decreasing bioavailability: intravenous >
intramuscular > subcutaneous > oral.

14. Advantages of non-per oral drug administration:

- Bypasses the first-pass effect
- Rapid onset of action
- Suitable for patients with swallowing difficulties or gastrointestinal issues

15. Drug disposition: The overall process involving drug absorption, distribution,
metabolism, and excretion.
Relationship between different processes of drug disposition: Absorption influences
distribution, metabolism affects elimination, and distribution impacts drug action.

16. Physiological barriers to drug distribution:

- Blood-brain barrier
- Placental barrier
- Intestinal epithelial barrier
- Blood-testis barrier
- Blood-ocular barrier

17. Factors responsible for drug distribution differences in patients of different age
groups:
- Variations in body composition (fat percentage, lean body mass)
- Differences in organ function and blood flow
- Altered protein binding capacity

18. Perfusion rate: The rate at which blood flows through a specific organ or tissue.
Highly perfused organs/tissues: Heart, liver, kidneys, brain
Moderately perfused organs/tissues: Skeletal muscle, skin
Poorly perfused organs/tissues: Bone, adipose tissue
19. Justification of the sentence: Distribution is a crucial step in the pharmacokinetics
of a drug because without proper distribution to the target tissues or site of action, the
drug cannot reach its intended site and initiate the pharmacological response.
Distribution ensures that the drug is transported to the tissues where it is needed to
exert its therapeutic effects.

20. Two major rate-determining steps in the distribution of drugs:

- Blood flow to tissues: The rate of drug distribution depends on the blood flow to
various organs and tissues.
- Permeability of membranes: The ability of a drug to cross cell membranes, such as
capillary walls or the blood-brain barrier, determines its distribution rate.
These rate-determining steps are applicable in determining the overall rate and extent
of drug distribution to different tissues.

21. [Diagrammatic representation of the placental barrier and blood flow across it.]

22. Apparent volume of distribution: It is a pharmacokinetic parameter that relates the

total amount of drug in the body to its plasma concentration. It indicates the degree of
drug distribution throughout the body and is calculated as the dose of the drug divided
by its plasma concentration.

23. Different drug-binding sites on human serum albumin:

- Sudlow site I (Warfarin binding site)
- Sudlow site II (Bilirubin binding site)
- Fatty acid binding sites
- Diazepam binding site

24. Plasma globulins identified for drug binding:

- Alpha-1-acid glycoprotein (AAG)
- Beta-lipoproteins
- Immunoglobulins (IgG)

25. Body components to which drugs normally bind:

- Plasma proteins (albumin and globulins)
- Tissues and organs (such as muscle and adipose tissue)
- Red blood cells

26. Factors influencing protein binding of drugs:

- Drug properties (lipid solubility, molecular weight, charge)
- Concentration of plasma proteins
- Disease states (e.g., liver or kidney dysfunction)
- Presence of other drugs that compete for binding sites

27. Factors affecting renal excretion:

- Glomerular filtration rate
- Tubular reabsorption
- Tubular secretion
- pH of urine
- Protein binding in the renal tubules

28. Clearance: The rate at which a drug is eliminated from the body, usually by renal
excretion. Renal clearance values reflect the combined processes of filtration,
reabsorption, and secretion in the kidneys.
29. Clearance ratio: The ratio of the clearance of a drug by a specific mechanism (e.g.,
renal clearance) to the total clearance of the drug from the body. Values of clearance
ratio help identify the relative contribution of a specific clearance mechanism to the
overall elimination of a drug.

30. Glomerular filtration: The process by which drugs are filtered from the blood into the
renal tubules. The glomerular filtration rate (GFR) is a measure of the rate at which the
kidneys filter the blood. Inulin and creatinine clearance are commonly used to estimate
GFR.

31. Extrarenal routes of drug excretion:

- Biliary excretion (into the bile)
- Pulmonary excretion (via exhaled air)
- Salivary excretion (into saliva)
- Mammary excretion (into breast milk)
- Sweat and tears

32. Biliary clearance: The elimination of drugs or their metabolites via the bile into the
intestines. Drugs excreted in bile can be classified based on their bile/plasma ratio into
high, moderate, or low excretion categories.

33. Effect of polarity and molecular weight on renal and biliary excretion behavior:
- Renal excretion: Polar and low-molecular-weight drugs are more likely to undergo
renal excretion.
- Biliary excretion: Lipophilic and high-molecular-weight drugs have a higher tendency
for biliary excretion.

34. Enterohepatic circulation of drugs: The process by which drugs are excreted into
the bile, enter the intestines, undergo reabsorption, and then return to the liver for
further metabolism. This process can prolong the duration of drug action and influence
the drug's pharmacokinetics.

35. Definitions:
- Bioavailability: The proportion of a drug that reaches systemic circulation and is
available to produce a pharmacological effect.
- Bioavailable fraction: The portion of a drug dose that reaches systemic circulation.
- Absolute bioavailability: The percentage of a drug that reaches systemic circulation
compared to intravenous administration.
- Relative bioavailability: A measure of how the bioavailability of a drug varies when
administered in different forms or routes compared to a reference standard.

36. Objectives of bioavailability studies: To determine the rate and extent of drug
absorption, compare different formulations or routes of administration, assess
bioequivalence, and guide dosing regimens for optimal therapeutic outcomes.

37. Methods for determining drug bioavailability:

- Pharmacokinetic studies in humans
- Comparative bioavailability studies
- In vitro dissolution testing
- Biopharmaceutical classification system (BCS) predictions

38. Definitions:
- Chemical equivalence: Two drug products contain the same active ingredients in the
same amounts, dosage form, and route of administration.
 - Pharmaceutic equivalence: Two drug products have the same active ingredients,
dosage form, strength, route of administration, and exhibit similar drug release
characteristics.
- Therapeutic equivalence: Two drug products produce similar therapeutic effects in
patients.
- Bioequivalence: Two drug products have comparable bioavailability and produce
similar pharmacokinetic and therapeutic effects.

39. Major approaches to enhance drug bioavailability:

- Formulation optimization (e.g., particle size reduction, solubility enhancement)
- Use of prodrugs
- Co-administration of absorption enhancers
- Modification of drug delivery systems (e.g., liposomes, nanoparticles)
- Pharmacokinetic/pharmacodynamic modeling and simulation

40. Physicochemical factors affecting oral bioavailability of a drug from its dosage
form:
- Solubility of the drug in gastrointestinal fluids
- Dissolution rate of the drug from the dosage form
- Particle size and surface area of the drug
- Chemical stability of the drug in the gastrointestinal tract
- Lipophilicity and hydrophilicity of the drug
- pH-dependent solubility and stability of the drug
- Drug formulation and excipients used in the dosage form

41. Absolute bioavailability: The percentage of a drug that reaches systemic circulation
after oral administration compared to intravenous administration.
Relative bioavailability: A measure of how the bioavailability of a drug varies when
administered in different forms or routes compared to a reference standard. The basic
difference is that absolute bioavailability compares oral and intravenous administration,
while relative bioavailability compares different forms or routes of administration.

42. [Diagrammatic representation of the blood-brain barrier.]

43. Human serum albumin (HSA) is considered versatile for drug binding due to its
abundant presence in plasma, high binding capacity, and ability to bind a wide variety of
drugs, including acidic and neutral compounds. It plays a significant role in drug
distribution and transport.

44. Protein binding and displacement interactions can influence the elimination half-life
of a drug. Increased protein binding can prolong the half-life, while displacement
interactions can increase the free drug fraction and potentially increase the elimination
rate.

45. Various sites of drug metabolism in the body include the liver (major site),
gastrointestinal tract, lungs, kidneys, and skin. The liver is considered a major site of
metabolism due to its high enzymatic activity and capacity to metabolize a wide range
of drugs.

46. Pharmacokinetics: The study of the time course of drug absorption, distribution,
metabolism, and excretion in the body.
Three pharmacokinetic parameters:
- Clearance: The rate at which a drug is eliminated from the body.
- Volume of distribution: The apparent volume in which a drug is distributed
throughout the body.
 - Half-life: The time required for the concentration of a drug in the body to decrease
by half.

47. [Illustration of a plasma concentration-time profile showing pharmacokinetic and

pharmacodynamic parameters after oral administration of a single dose of a drug.]

48. Pharmacokinetic models are important and useful for predicting drug
concentrations in different body compartments over time, optimizing dosing regimens,
assessing drug interactions, and guiding drug development and therapeutic monitoring.

49. Compartment modeling: A mathematical approach that divides the body into
discrete compartments to describe drug distribution and elimination. It helps in
understanding the pharmacokinetics of drugs in different tissues or compartments.

50. Advantages of compartment modeling:

- Provides a simplified representation of drug behavior in the body
- Allows estimation of pharmacokinetic parameters
- Facilitates prediction of drug concentrations in different compartments
- Useful for dose optimization and therapeutic drug monitoring

51. Disadvantages of compartment modeling:

- Assumes homogeneity within compartments, which may not be accurate in reality
- Requires multiple blood samples for parameter estimation
- Limited ability to capture complex drug disposition processes
- May not fully account for interindividual variability in drug response

52. Non-compartmental analysis: An alternative approach to pharmacokinetic analysis

that does not rely on compartmental models. It involves directly analyzing drug
concentration-time data to estimate pharmacokinetic parameters.
Advantages of non-compartmental analysis:
- Does not require assumptions of compartmental distribution
- Can handle complex dosing regimens
- Suitable for sparse or limited sampling data
- Allows estimation of additional parameters like area under the curve (AUC)

53. [Schematic representation of physiologic pharmacokinetic models.]

54. Advantages of physiologic models over compartment models:

- Physiologic models incorporate the anatomical and physiological characteristics of
the body, providing a more realistic representation of drug behavior.
- They can capture the complexities of drug distribution and elimination processes
more accurately.
- Physiologic models can simulate the effects of physiological changes or disease
conditions on drug pharmacokinetics.

55. Elimination half-life: The time required for the concentration of a drug in the body to
decrease by half during the elimination phase.
Total body clearance: The rate at which a drug is completely removed from the body,
usually expressed as the volume of plasma cleared of the drug per unit of time.

56. Multicompartment model: A pharmacokinetic model that divides the body into
multiple compartments to describe drug distribution and elimination. Two-
compartment models can be categorized based on the compartment from which the
drug is eliminated, such as central compartment elimination or peripheral compartment
elimination.
57. In a two-compartment model, the central compartment represents the plasma or
highly perfused tissues, while the peripheral compartment represents tissues with
slower drug distribution kinetics or less perfusion.

58. Loading dose: A higher initial dose of a drug given to achieve therapeutic levels
quickly.
Maintenance dose: The regular, repeated dose of a drug required to maintain a
desired therapeutic concentration in the body.

59. [Schematic representation of changes in drug concentration in the central (plasma)

and peripheral compartments after IV bolus administration.]

60. Dose-dependent pharmacokinetics: When the pharmacokinetics of a drug change in

a dose-dependent manner, leading to non-linear relationships between dose and drug
concentrations in the body.
Test to detect nonlinearity in pharmacokinetics: Comparison of drug concentration-
time profiles after administration of different doses of the drug.

61. Nonlinear pharmacokinetics: When the pharmacokinetics of a drug are not

proportional to the dose administered. Causes of nonlinearity in drug absorption
include saturation of absorption processes, non-linear protein binding, or saturation of
metabolism or elimination pathways.

62. Nonlinear pharmacokinetics: Nonlinearity in drug distribution can occur due to

saturable binding to tissues or organs, changes in blood flow, or nonlinear permeability
across membranes. Examples include saturable hepatic extraction and nonlinear
distribution in tissues with limited blood flow, like adipose tissue.

63. Causes of nonlinearity in drug metabolism: Saturation of metabolic enzymes,

induction or inhibition of metabolic enzymes, and genetic polymorphisms.

64. Linear pharmacokinetics: Drug follows first-order kinetics, clearance remains

constant, and increasing dose leads to proportional increase in concentration.

65.Nonlinear pharmacokinetics: Drug does not follow first-order kinetics, clearance is

not constant, and increasing dose may result in disproportional increase in
concentration.

65. Phase II biotransformation reactions: Glucuronidation, sulfation, methylation,

acetylation, and glutathione conjugation.
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