Diese Präsentation wurde erfolgreich gemeldet.
Wir verwenden Ihre LinkedIn Profilangaben und Informationen zu Ihren Aktivitäten, um Anzeigen zu personalisieren und Ihnen relevantere Inhalte anzuzeigen. Sie können Ihre Anzeigeneinstellungen jederzeit ändern.

Elimination kinetics

2.238 Aufrufe

Veröffentlicht am

routes of excretion of drugs with special focus on elimination kinetics.Pharmacokinetic parameters explaines and graphs included.

Veröffentlicht in: Bildung
  • Als Erste(r) kommentieren

Elimination kinetics

  1. 1. ELIMINATION KINETICS Dr. Lily Dubey Assistant Professor Dept. of Pharmacology Dr. D Y Patil Medical College
  2. 2. 9/27/2017Eliminationkinetics 2
  3. 3. ROUTES OF DRUG EXCRETION  Hydrophilic compounds can be easily excreted  Liver  Kidney  Sweat and saliva  Milk  Pulmonary 9/27/2017 3 Eliminationkinetics
  4. 4. HEPATIC EXCRETION  Drugs can be excreted in bile, especially when the are conjugated with – glucuronic Acid Portal vein Bile duct Intestines 9/27/2017 4 Eliminationkinetics
  5. 5. ENTEROHEPATIC CYCLING  Eg. steroid hormones, rifampicin, amoxycillin, contraceptives 9/27/2017 5 Eliminationkinetics Drug is absorbed glucuronidated or sulfatated in the liver and secreted through the bile glucuronic acid/sulfate is cleaved off by bacteria in GI tract drug is reabsorbed
  6. 6. RENAL EXCRETION  Glomerular Filtration  Depends on their plasma protein binding and renal blood flow  Tubular Reabsorption  Back diffusion of Drugs (99%) – lipid soluble drugs  Depends on pH of urine, ionization  Tubular Secretion  Energy dependent  Utilized clinically – penicillin Vs probenecid, probenecid Vs uric acid (salicylate)  Quinidine decreases renal and biliary clearance of digoxin by inhibiting efflux carrier P-gp 9/27/2017 6 Eliminationkinetics
  7. 7. KINETICS OF ELIMINATION  Pharmacokinetics - F, V, CL, t1/2  Clearance: volume of plasma from which drug is completely removed in unit time CL = Rate of elimination /C 9/27/2017 7 Eliminationkinetics
  8. 8. PLASMA HALF-LIFE  Defined as time taken for its plasma concentration to be reduced to half of its original value – t1/2 = In2/k In2 = natural logarithm of 2 (0.693) k = elimination rate constant Elimination rate constant = CL / V t1/2 = 0.693 x V / CL CL = RoE/C V = dose IV/C 9/27/2017 8 Eliminationkinetics
  9. 9. PLASMA HALF-LIFE 1 half-life …………. 50% 2 half-lives………… 25% 3 half-lives …….…..12.5% 4 half-lives ………… 6.25% 50 + 25 + 12.5 + 6.25 = 93.75 93.75 + 3.125 + 1.56 = 98% after 5 HL 9/27/2017 9 Eliminationkinetics
  10. 10. REPEATED DOSING  At steady state, elimination = input Dose Rate = target Cpss x CL Oral administration Dose rate = target Cpss x CL/F Zero order kinetics: Michaelis Menten kinetics RoE = (Vmax) (C) / Km + C Vmax = max. rate of drug elimination Km = Plasma conc at which elimination rate is half maximal CL = Roe/C 9/27/2017 10 Eliminationkinetics
  11. 11. THE PLATUE PRINCIPLE Repeated dosing: • When constant dose of a drug is repeated before the expiry of 4 half-life – peak concentration is achieved after certain interval • Balances between dose administered and dose interval 9/27/2017 11 Eliminationkinetics
  12. 12. STEADY STATE CONCENTRATION 9/27/2017 12 Eliminationkinetics Peaks and troughs
  13. 13. KINETICS OF ELIMINATION 9/27/2017 13 Eliminationkinetics
  14. 14. 9/27/2017 14 Eliminationkinetics
  15. 15. KINETICS OF IV DOSING 9/27/2017 15 Eliminationkinetics
  16. 16. KINETICS OF ELIMINATION 9/27/2017 16 Eliminationkinetics FIRST ORDER ZERO ORDER Drug eliminated in unit time Constant fraction Constant amount Nature Elimination proportional to drug concentration Elimination saturates at higher concentration Plasma concentration – time curve Exponential decay Linear decay On log scale linear Non- linear kinetics Linear kinetics Non linear kinetics Drugs Most drugs(95%) Alcohol, aspirin, warfarin, theophylline
  17. 17. TARGET LEVEL STRATEGY  Low safety margin drugs (anticonvulsants, antidepressants, Lithium, Theophylline – maintained at certain concentration within therapeutic range  Drugs with short half-life (2-3 Hrs) –administered at conventional intervals (6-12 Hrs) – fluctuations are therapeutically acceptable  Long acting drugs:  Loading dose: Single dose or repeated dose in quick succession – to attain target conc. Quickly Loading dose = target Cp X V/F  Maintenance dose: dose to be repeated at specific intervals Maintanace dose = ssPC X Clearance/F 9/27/2017 17 Eliminationkinetics
  18. 18. THERAPEUTIC DRUG MONITORING(TDM)  Useful in  Narrow safety margin drugs – digoxin, anticonvulsants, antiarrhythmics and aminoglycosides  Large individual variation – lithium and antidepressants  Renal failure cases  Poisoning cases  Not useful in  Response measurable drugs – antihypertensives  Drugs activated in body – levodopa  Hit and run drugs – Reseprpine, MAO inhibitors  Irreversible action drugs – Organophosphorous compounds 9/27/2017 18 Eliminationkinetics
  19. 19. 9/27/2017 19 Eliminationkinetics

×