Updated: 7/14/2017

Pharmacokinetics

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Volume of Distribution (Vd)
  • Volume of distribution (Vd) relates amount of drug in body to plasma concentration
  • Vd = (amount of drug in the body) / (plasma drug concentration)
  • Vd is changed in disease states that decrease plasma proteins
    • a decrease in plasma proteins decreases binding of drug to plasma proteins
      • Vd of drugs
    • e.g., liver disease
      • via ↓ protein synthesis
    • e.g., kidney disease
      • via urinary protein loss
  • Vd predicts drug distribution in body
    • low Vd drugs
      • 4-8 L
      • drugs distribute in vascular compartment (blood) and bind plasma proteins
      • drugs are large and/or charged molecules
    • medium Vd drugs
      • drugs distribute in extracellular compartment and/or total body water
      • drugs are small, hydrophilic molecules that do not bind plasma proteins
    • high Vd drugs
      • > body weight
      • drugs distribute in all tissues
      • drugs are small, lipophilic molecules that bind strongly to extravascular proteins
Clearance (CL)
  • CL = (rate of elimination of drug) / (plasma drug concentration) = Vd * Ke
    • Ke = elimination constant
  • CL relates the rate of elimination to the plasma concentration
Half-Life (t1/2)
  • t1/2 = (0.7 * Vd)/CL
  • half-life is time required for amount of drug to fall to 50% of an earlier measurement during elimination or during constant infusion
    • a drug infused at a constant rate reaches about 94% of steady state after 4 half lives  
  • for drugs eliminated by first-order kinetics, half-life is constant regardless of concentration
# of half lives 1 2 3 4
Concentration 50% 75% 87.5% 93.75% 
Bioavailability (F)
  • bioavailability is the fraction of administered dose that reaches systemic circulation
  • bioavailability is defined as unity, or 100%, in case of IV administration
  • bioavailability of drug administered by other routes is generally reduced by incomplete absorption, first-pass metabolism, and any distribution into other tissues that occurs before the drug enters systemic circulation
    • e.g., orally, F = percent that is absorbed and survives first-pass metabolism in liver
  • Calculation of bioavailabillity (F) = 100% * (AUC-oral * Dose-IV) / (AUC-IV * Dose-oral), where AUC is the area under the curve of a pharmacokinetic plasma concentration versus time plot  
 

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Lab Values
Blood, Plasma, Serum Reference Range
ALT 8-20 U/L
Amylase, serum 25-125 U/L
AST 8-20 U/L
Bilirubin, serum (adult) Total // Direct 0.1-1.0 mg/dL // 0.0-0.3 mg/dL
Calcium, serum (Ca2+) 8.4-10.2 mg/dL
Cholesterol, serum Rec: < 200 mg/dL
Cortisol, serum 0800 h: 5-23 μg/dL //1600 h:
3-15 μg/dL
2000 h: ≤ 50% of 0800 h
Creatine kinase, serum Male: 25-90 U/L
Female: 10-70 U/L
Creatinine, serum 0.6-1.2 mg/dL
Electrolytes, serum  
Sodium (Na+) 136-145 mEq/L
Chloride (Cl-) 95-105 mEq/L
Potassium (K+) 3.5-5.0 mEq/L
Bicarbonate (HCO3-) 22-28 mEq/L
Magnesium (Mg2+) 1.5-2.0 mEq/L
Estriol, total, serum (in pregnancy)  
24-28 wks // 32-36 wks 30-170 ng/mL // 60-280 ng/mL
28-32 wk // 36-40 wks 40-220 ng/mL // 80-350 ng/mL
Ferritin, serum Male: 15-200 ng/mL
Female: 12-150 ng/mL
Follicle-stimulating hormone, serum/plasma Male: 4-25 mIU/mL
Female: premenopause: 4-30 mIU/mL
midcycle peak: 10-90 mIU/mL
postmenopause: 40-250
pH 7.35-7.45
PCO2 33-45 mmHg
PO2 75-105 mmHg
Glucose, serum Fasting: 70-110 mg/dL
2-h postprandial:<120 mg/dL
Growth hormone - arginine stimulation Fasting: <5 ng/mL
Provocative stimuli: > 7ng/mL
Immunoglobulins, serum  
IgA 76-390 mg/dL
IgE 0-380 IU/mL
IgG 650-1500 mg/dL
IgM 40-345 mg/dL
Iron 50-170 μg/dL
Lactate dehydrogenase, serum 45-90 U/L
Luteinizing hormone, serum/plasma Male: 6-23 mIU/mL
Female: follicular phase: 5-30 mIU/mL
midcycle: 75-150 mIU/mL
postmenopause 30-200 mIU/mL
Osmolality, serum 275-295 mOsmol/kd H2O
Parathyroid hormone, serume, N-terminal 230-630 pg/mL
Phosphatase (alkaline), serum (p-NPP at 30° C) 20-70 U/L
Phosphorus (inorganic), serum 3.0-4.5 mg/dL
Prolactin, serum (hPRL) < 20 ng/mL
Proteins, serum  
Total (recumbent) 6.0-7.8 g/dL
Albumin 3.5-5.5 g/dL
Globulin 2.3-3.5 g/dL
Thyroid-stimulating hormone, serum or plasma .5-5.0 μU/mL
Thyroidal iodine (123I) uptake 8%-30% of administered dose/24h
Thyroxine (T4), serum 5-12 μg/dL
Triglycerides, serum 35-160 mg/dL
Triiodothyronine (T3), serum (RIA) 115-190 ng/dL
Triiodothyronine (T3) resin uptake 25%-35%
Urea nitrogen, serum 7-18 mg/dL
Uric acid, serum 3.0-8.2 mg/dL
Hematologic Reference Range
Bleeding time 2-7 minutes
Erythrocyte count Male: 4.3-5.9 million/mm3
Female: 3.5-5.5 million mm3
Erythrocyte sedimentation rate (Westergren) Male: 0-15 mm/h
Female: 0-20 mm/h
Hematocrit Male: 41%-53%
Female: 36%-46%
Hemoglobin A1c ≤ 6 %
Hemoglobin, blood Male: 13.5-17.5 g/dL
Female: 12.0-16.0 g/dL
Hemoglobin, plasma 1-4 mg/dL
Leukocyte count and differential  
Leukocyte count 4,500-11,000/mm3
Segmented neutrophils 54%-62%
Bands 3%-5%
Eosinophils 1%-3%
Basophils 0%-0.75%
Lymphocytes 25%-33%
Monocytes 3%-7%
Mean corpuscular hemoglobin 25.4-34.6 pg/cell
Mean corpuscular hemoglobin concentration 31%-36% Hb/cell
Mean corpuscular volume 80-100 μm3
Partial thromboplastin time (activated) 25-40 seconds
Platelet count 150,000-400,000/mm3
Prothrombin time 11-15 seconds
Reticulocyte count 0.5%-1.5% of red cells
Thrombin time < 2 seconds deviation from control
Volume  
Plasma Male: 25-43 mL/kg
Female: 28-45 mL/kg
Red cell Male: 20-36 mL/kg
Female: 19-31 mL/kg
Cerebrospinal Fluid Reference Range
Cell count 0-5/mm3
Chloride 118-132 mEq/L
Gamma globulin 3%-12% total proteins
Glucose 40-70 mg/dL
Pressure 70-180 mm H2O
Proteins, total < 40 mg/dL
Sweat Reference Range
Chloride 0-35 mmol/L
Urine  
Calcium 100-300 mg/24 h
Chloride Varies with intake
Creatinine clearance Male: 97-137 mL/min
Female: 88-128 mL/min
Estriol, total (in pregnancy)  
30 wks 6-18 mg/24 h
35 wks 9-28 mg/24 h
40 wks 13-42 mg/24 h
17-Hydroxycorticosteroids Male: 3.0-10.0 mg/24 h
Female: 2.0-8.0 mg/24 h
17-Ketosteroids, total Male: 8-20 mg/24 h
Female: 6-15 mg/24 h
Osmolality 50-1400 mOsmol/kg H2O
Oxalate 8-40 μg/mL
Potassium Varies with diet
Proteins, total < 150 mg/24 h
Sodium Varies with diet
Uric acid Varies with diet
Body Mass Index (BMI) Adult: 19-25 kg/m2
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(M1.PH.89) A 65-year-old female patient with a past medical history of diabetes mellitus and an allergy to penicillin develops an infected abscess positive for MRSA on the third day of her hospital stay. She is started on an IV infusion of vancomycin at a dose of 1000 mg every 12 hours. Vancomycin is eliminated by first-order kinetics and has a half life of 6 hours. The volume of distribution of vancomycin is 0.5 L/kg. Assuming no loading dose is given, how long will it take for the drug to reach 94% of its plasma steady state concentration? Review Topic

QID: 100605
1

6 hours

3%

(9/266)

2

12 hours

13%

(34/266)

3

18 hours

19%

(51/266)

4

24 hours

52%

(137/266)

5

30 hours

8%

(20/266)

M1

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PREFERRED RESPONSE 4

(M1.PH.75) An experimental infusable drug, X729, is currently being studied to determine its pharmacokinetics. The drug was found to have a half life of 1.5 hours and is eliminated by first order kinetics. What is the minimum number of hours required to reach a steady state concentration of >90%? Review Topic

QID: 106861
1

1.5

2%

(2/85)

2

3

9%

(8/85)

3

4.5

25%

(21/85)

4

6

58%

(49/85)

5

7.5

2%

(2/85)

M1

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PREFERRED RESPONSE 4

(M1.PH.75) A pharmaceutical company is attempting to determine the bioavailability of a new glucose-lowering agent, Compound X, they have developed. They have previously studied the pharmacokinetics of both IV and oral forms of this drug. The company has obtained the following information regarding the IV formulation of Compound X: Administration of 50 mg of Compound X by IV yields an area under the curve (AUC) on a plasma drug concentration versus time plot of 60 mg hr/L. Additionally, the company has also obtained the following information regarding the oral formulation of Compound X: Administration of 100 mg of Compound X by a PO route yields an AUC on a plasma drug concentration versus time plot of 80 mg hr/L. Which of the following is the absolute bioavailability of Compound X? Review Topic

QID: 106854
1

58%

4%

(6/148)

2

64%

11%

(17/148)

3

67%

48%

(71/148)

4

70%

18%

(26/148)

5

74%

11%

(17/148)

M1

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PREFERRED RESPONSE 3
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