p.7
Kinetics of Elimination
What is zero-order kinetics in drug elimination?
A constant amount of drug is absorbed or eliminated per time interval.
p.19
Impact of Dosage on Pharmacokinetics
What is the effect of administering the same dose at higher intervals on plasma concentration?
The plasma concentration decreases.
p.19
Impact of Dosage on Pharmacokinetics
What factor is illustrated by M. Vindelbo's graph regarding plasma concentration?
Changes in plasma concentration in response to changes in the administration interval and the dose.
p.6
Intravenous vs Oral Administration
What is more predictable with intravenous (i.v.) drug administration compared to other routes?
Drug concentration in the blood.
p.7
Kinetics of Elimination
What characterizes first-order kinetics in drug elimination?
Drugs are absorbed or eliminated concentration-dependently, following an exponential function.
p.13
Elimination Half-Life (t1/2) and Clearance (Cl)
How is the elimination half-life (t1/2) of chloramphenicol determined?
It is borrowed from M. Vindelbo's lecture graph and is 1 hour.
p.8
Volume of Distribution (Vd) Calculation
What are the average compositions of plasma, extracellular, and total body water in a dog?
The average compositions are: plasma - 4%, extracellular - 17%, and total body water - 58%.
p.16
Renal Excretion and Dose Adjustments
Is renal excretion the main route of elimination for chloramphenicol?
No, renal excretion is not the main route of elimination for chloramphenicol.
p.10
Volume of Distribution (Vd) Calculation
What are the percentages of plasma, extracellular, and total body water in a dog's body weight?
Plasma: 4%, Extracellular: 17%, Total body water: 58%
p.11
Volume of Distribution (Vd) Calculation
What might cause a drug not to distribute uniformly?
Sequestering at a site outside the plasma volume and its ability to readily cross membranes and distribute to different tissues.
p.16
Renal Excretion and Dose Adjustments
Would dose adjustments be necessary for a patient with compromised renal capacity when taking chloramphenicol?
Yes, dose adjustments can be necessary depending on the level of impairment, interval of administration, and length of treatment to avoid drug accumulation and intoxication, especially for drugs with a low therapeutic index (TI).
p.15
Elimination Half-Life (t1/2) and Clearance (Cl)
When is the half-life of a drug ideally determined?
The half-life of a drug is ideally determined after intravenous (IV) administration.
p.12
Bioavailability (F) Estimation
How do you estimate the bioavailability (F) of chloramphenicol?
By using the formula F = (AUCp.o. / AUCi.v.) * 100.
p.21
Pharmacokinetics Overview
What is the focus of Chatterjee et al.'s pharmacokinetic characterization?
Pharmacokinetic characterization of drugs and new product development.
p.8
Volume of Distribution (Vd) Calculation
What does the apparent volume of distribution (Vd) reflect in terms of drug distribution in body compartments?
The Vd reflects how extensively a drug distributes into body compartments. A high Vd indicates extensive distribution into tissues, while a low Vd suggests the drug remains largely within the plasma.
p.10
Volume of Distribution (Vd) Calculation
How is the concept of Vd described?
Vd is a virtual volume that describes the apparent volume in which the drug is distributed.
p.20
Pharmacokinetics Overview
Why is blood concentration important in pharmacokinetics?
It determines the drug's efficacy and safety, ensuring it stays within the therapeutic window.
p.17
Elimination Half-Life (t1/2) and Clearance (Cl)
Would you expect a change in the elimination half-life (t1/2) when comparing 25 mg/kg to 50 mg/kg administration of chloramphenicol?
No, but the duration of the effect would be affected.
p.11
Impact of Dosage on Pharmacokinetics
What are some examples of drugs that can be retained in deep compartments, leading to long-term ADRs?
Amiodarone (antiarrhythmic), tetracyclines, and thiopental.
p.5
Impact of Dosage on Pharmacokinetics
What is considered the therapeutic window for the drug mentioned?
The therapeutic window is 10 - 25 mg/L.
p.7
Kinetics of Elimination
Can you give an example of substances that follow zero-order kinetics in elimination?
Ethanol (EtOH) for elimination.
p.3
Chloramphenicol as an Antimicrobial Agent
What types of microorganisms does chloramphenicol target?
Chloramphenicol targets Gram-positive bacteria, Gram-negative bacteria, and anaerobic microorganisms.
p.11
Volume of Distribution (Vd) Calculation
What does a distribution volume higher than the total body water (>80 L) suggest?
It points to deep compartments.
p.5
Pharmacokinetics Overview
What does t max represent in pharmacokinetics?
t max represents the time it takes to reach the maximum concentration of the drug in the blood after administration.
p.15
Elimination Half-Life (t1/2) and Clearance (Cl)
Is the half-life (t1/2) affected by the route of administration?
No, the half-life (t1/2) does not change significantly.
p.3
Chloramphenicol as an Antimicrobial Agent
What type of agent is chloramphenicol?
Chloramphenicol is an antimicrobial agent.
p.9
Volume of Distribution (Vd) Calculation
How do you calculate Vd using dose and Cp₀?
Vd = 825 mg / 45 μg/mL = 825 mg / 0.045 mg/mL = 18,333 mL = 18.3 L.
p.3
Intravenous vs Oral Administration
How was the content of microbiologically active material in the samples analyzed?
The content was analyzed by bioassay for unchanged chloramphenicol.
p.5
Impact of Dosage on Pharmacokinetics
How can you determine the duration for which the drug would be effective after oral administration?
The drug would be effective as long as its concentration in the blood remains within the therapeutic window (10 - 25 mg/L).
p.19
Impact of Dosage on Pharmacokinetics
What happens to plasma concentration when higher doses are administered at the same interval?
The plasma concentration increases.
p.16
Renal Excretion and Dose Adjustments
Why could dose adjustments be necessary in patients with compromised renal capacity?
Because impaired renal function could lead to drug accumulation and intoxication, especially for drugs with a low therapeutic index (TI).
p.15
Intravenous vs Oral Administration
What is the advantage of determining the half-life of a drug after IV administration?
The entire dose of the drug is immediately available for metabolism and excretion.
p.10
Volume of Distribution (Vd) Calculation
How is the apparent volume of distribution (Vd) expressed in terms of body weight?
0.04, 0.17, and 0.58 L/kg for plasma, extracellular, and total body water respectively
p.11
Impact of Dosage on Pharmacokinetics
Why are deep compartments problematic in pharmacotherapy?
Because they point to retention of a drug in the organism, such as in adipose tissue or bone, which can cause long-term adverse drug reactions (ADRs).
p.18
Dosing Rate and Maintenance Dose Calculation
How do you calculate the dosing rate for an intravenous (i.v.) infusion to achieve the target concentration?
Dosing rate = Cl x Target concentration (TC).
p.13
Elimination Half-Life (t1/2) and Clearance (Cl)
What does the elimination half-life (t1/2) represent?
The time taken by the drug to reduce to 50% of its initial concentration.
p.8
Volume of Distribution (Vd) Calculation
How do you calculate the apparent volume of distribution (Vd) of chloramphenicol in a 16.5 kg dog?
The apparent volume of distribution (Vd) can be calculated using the formula: Vd = (dose of drug) / (plasma concentration of drug). Details specific to chloramphenicol and the 16.5 kg dog would be needed for exact calculation.
p.15
Intravenous vs Oral Administration
How does oral administration affect the half-life of a drug?
The value of the half-life will be increased in proportion to the delay in absorption, such as in extended release formulations.
p.17
Impact of Dosage on Pharmacokinetics
How does a lower dose (25 mg/kg) of chloramphenicol administration affect the Area Under the Curve (AUC) compared to a higher dose (50 mg/kg)?
The Area Under the Curve (AUC) would be smaller with a lower dose.
p.4
Intravenous vs Oral Administration
How does the mode of administration differ between Dog 1 and Dog 2?
Dog 1 received the drug intravenously, while Dog 2 received it orally.
p.15
Impact of Dosage on Pharmacokinetics
Which pharmacokinetic parameters can change with different routes of administration even if the half-life does not?
tmax, Cmax, and duration of action can change.
p.9
Volume of Distribution (Vd) Calculation
How do you find Cp₀ from the equation ln(x) = 3.8?
Solve for x: x ≈ 45 μg/mL.
p.20
Pharmacokinetics Overview
What is therapeutic window?
The range of drug doses which can treat disease effectively while staying within the safety range.
p.5
Pharmacokinetics Overview
What does C max represent in pharmacokinetics?
C max represents the maximum concentration of the drug in the blood after administration.
p.19
Impact of Dosage on Pharmacokinetics
How does administering half the dose at half the interval affect plasma concentration?
It maintains a more consistent plasma concentration.
p.10
Volume of Distribution (Vd) Calculation
What does a Vd greater than the body volume of water indicate about drug distribution?
It indicates extensive distribution of the drug beyond the body water compartments.
p.20
Kinetics of Elimination
What is the difference between 1st order and 0 order kinetics?
In 1st order kinetics, the rate of drug metabolism is proportional to the drug concentration, while in 0 order kinetics, the rate is constant regardless of concentration.
p.8
Volume of Distribution (Vd) Calculation
How can the distribution of chloramphenicol be assessed in the body compartments of a dog?
By comparing the Vd with the volumes of plasma, extracellular fluid, and total body water, one can infer whether the drug distributes primarily in the plasma, extracellular fluid, or throughout the entire body.
p.12
Bioavailability (F) Estimation
What are the AUC values provided for chloramphenicol administered orally and intravenously?
AUCp.o. = 83 µg.hr/ml and AUCi.v. = 70 µg.hr/ml.
p.10
Volume of Distribution (Vd) Calculation
How does the Vd of chloramphenicol in a 16.5 kg dog compare with the dog's body volume of water?
The Vd of 18.3 L is greater than the total body water of the dog.
p.20
Pharmacokinetics Overview
How does time affect blood concentration of a drug?
Over time, the drug's concentration in the blood will rise to a peak level after administration and then decline as the body metabolizes and eliminates it.
p.9
Pharmacokinetics Overview
What does the Y-intercept represent in pharmacokinetics?
Cp₀ (initial plasma concentration).
p.11
Volume of Distribution (Vd) Calculation
What does a distribution volume approximately equal to the total body water (70-80 L in a 70kg human) imply?
It indicates that the drug is distributed in the entire organism.
p.5
Impact of Dosage on Pharmacokinetics
How do you determine the initiation of the drug's effect after oral administration?
The drug's effect initiation occurs when its concentration reaches the lower limit of the therapeutic window (10 mg/L).
p.12
Bioavailability (F) Estimation
Why might the calculated bioavailability of chloramphenicol exceed 100%?
The data might have been extracted from different dogs for oral and IV administration.
p.18
Dosing Rate and Maintenance Dose Calculation
How do you calculate the maintenance dose for oral administration?
Maintenance Dose = Dosing rate x Dosing interval / F.
p.12
Bioavailability (F) Estimation
What is the theoretical maximum bioavailability of a drug?
Theoretically, bioavailability cannot exceed 100% (F > 1 is not possible).
p.20
Impact of Dosage on Pharmacokinetics
What should you do if you skip or forget to take a dose of medication?
Follow the instructions given by your healthcare provider, which may include taking the missed dose as soon as you remember or skipping it if it's close to the next scheduled dose.
