Pharmacokinetics and Therapeutics of Drugs - Lab Report Example

Pharmacokinetics & Therapeutics of Drugs" Pharmacokinetics is studied as LADME. Liberation, Absorption, Distribution, Metabolism and Excretion of thedrug. In the present case patient was medicated with the following drugs: 1. Atenolol 2. Irbesartan 3. Pantoprazole 4. Mixtard 30/70 5. Thyroxine 6. Paracetamol/ codeine Pharmacokinetics of Atenolol: Liberation: Chemical name: 2-[4-(2-hydroxy-3-isopropyl-aminopropoxy) phenyl acetamide. Molecular formula: C14H22N2O3. MW: 266.3. CAS: 2912268-7. Atenolol is structurally similar to propranolol but bears substitution on the aromatic ring. Pharmacology of Atenolol: Atenolol is a beta-adrenoreceptor blocking drug acting on the beta-receptors in the heart. As the dose is increased, selectivity diminishes. Atenolol displays small essential sympathomimetic action but does not display any kind of membrane stabilising actions. The drug is capable of reducing the enhanced blood pressure and also acts as inhibiting factor for tachycardia. It also reduces plasma rennin concentration. These inhibiting actions are co-related with blood levels and not with plasma deliberation or hypertensive effects. Atenolol is well absorbed and highly effective in most of the population. Mechanism of Action: Antianginal action of Atenolol is attributed to the diminution action of left ventricle and also consumption of oxygen which occurs due to reduced heart rate. Antiarrhythmic effect of Atenolol is attributed to its anti-sympathetic consequences, as the drug lowers SA node, AV node role rather it prolongs atrial- refractory episode, although it does not show any role in electrophysiological properties of the HIS-Purkinje system. Pharmacokinetics: Absorption of Atenolol ranges from 40 to 60%, it fundamentally lacks hepatic metabolism. Distribution & Metabolism: Atenolol peaks are observed in 2- 4hrs in blood after a single 100 mg oral dose with the concentration of 0.4 to 0.9 microgram/ml. Atenolol is dispersed throughout the tissues and fewer than 10% of the dosage is metabolised. Excretion: Urinary metabolite identified are hydroxyl derivative. Route of removal is renal excretion. The plasma half-life, calculated through blood level decay or urinary build up, is about 7- 9 hours. Patients suffering from any kind of renal damage display a progressive persistence of the half-life. Individuals with normal renal function display lasting therapeutic effect as the drug is capable of controlling the rise in blood pressure 24 hours followed by 50 mg oral dose (Wan, 1979). Pharmacokinetics of Pantoprazole: Liberation: Chemical name: (RS)-6-(difluoromethoxy)-2-[(3,4-dimethoxypyridin-2-yl)methylsulfinyl]-1H-benzo[d]imidazole. A proton pump inhibitor. To handle acid-related gastrointestinal diseases encompassing reflux esophagitis, duodenal and gastric ulcers. Absorption: It is an inactive pro-drug to protect acid labile drug from rapid destruction within gastric lumen, it is formulated as delayed release acid-resistant, enteric coated capsules or tablets. After passing through the stomach into alkaline intestinal lumen, the enteric coating is dissolved and the pro-drug is dissolved. Mechanism: At acidic pH less than 5, it is activated to two charged cationic forms (sulphenamide and sulphenic acid) that reacts covalently with SH groups of H+ K+ ATPase enzyme and inactivates it irreversibly. Pharmacokinetics: Pantoprazole, managed as a 40 mg enteric coated tablet, is quantitatively captivated. Its bioavailability is 77% and undergoes no change even on numerous dosing. Single oral dose of 40 mg, approximates 2.5 mg/l, with a tmax of 2-3 h. The AUC(O,inf.) is approximately 5 mgxh/l. It shows linear pharmacokinetics after IV as well as oral administration. Metabolism: Pantoprazole undergoes hepatic metabolism, has a total serum clearance of 0.1 l/h/kg, a serum exclusion half life around 1.1 h, and an noticeable capacity of allocation of 0.15 l/kg. It is that reported that 98% of pantoprazole is bound to serum proteins. Serum metabolite is by demethylation at the 4-position of the pyridine ring, trailed by conjugation with sulphate. 80% of an oral or intravenous dose is excreted as metabolites in urine; while the remaining is excreted in faeces from biliary secretion. The pharmacokinetics of pantoprazole remains unchanged in patients with renal failure. Excretion: The clearance of pantoprazole is not significantly affected by age, its half-life being approximately 1.25 h in the elderly. Associated ingestion of food had no control on the bioavailability of pantoprazole. Interaction: Pantoprazole demonstrates lack of cytochrome P450 interaction with concurrently administered drugs (Huber,1996) Pharmacokinetics of Irbesartan: The drug does not affect the pharmacokinetics of other drugs. Absorption. The oral bioavailability of Irbesartan calculated following administration of Avapro HCT are related to the bioavailability of Irbesartan. The complete oral bioavailability of Irbesartan is 60 - 80% . Plasma concentrations shows its peak at 1.5 - 2 hours following oral administration of Irbesartan. Distribution: 90% of Irbesartan binds to plasma, and does not bind to the cellular components of blood. The capacity of allocation is 53 - 93 L (0.72 to 1.24 L/kg). Metabolism: Only 20% of Irbesartan is absorbed while 80% circulates in blood. The drug undergoes hepatic metabolism via glucuronide conjugation and oxidation. Thus the major circulating metabolite is Irbesartan glucuronide (around 6%). Oxidation is carried out by Cyt P450 isoenzyme CYP2C9. Metabolism of this drug is not induced nor inhibited by other isozymes. Irbesartan does not induce nor inhibit isoenzyme CYP3A4. Excretion: Irbesartan and its metabolites are excreted through biliary as well as renal courses. 20% is eliminated through urine while rest through faeces. Less than 2% of the dose is excreted in urine as unaffected Irbesartan. The terminal removal half-life (t1/2) of Irbesartan from plasma is 11 - 15 hours. The entire body elimination of intravenously governed Irbesartan is 157 - 176 ml/minute, of which 3.0 - 3.5 m/minute is renal clearance. Irbesartan exhibits linear pharmacokinetics over the therapeutic dose range. Steady-state plasma concentrations are attained within three days after initiation of a once daily dosing regimen. Limited accumulation (< 20%) is observed in plasma upon repeated once daily dosing (Marino, 2001; Katzung, 2009). Pharmacokinetics of Mixtard 30/70 A mixture of highly purified pork regular insulin 30% and isophane insulin 70%. Mixtard 30/70. Mixtard 30/70 is an transitional performing human insulin preparation. The hypoglycaemic consequence following subcutaneous management starts within 0.5 hours, and reaches its peak from 2 -12 hours and diminishes in 24 hours. Mixtard 30/70 is not precisely correspondent to its constituent insulins (Howland, 2006; Verzijl, 2000). Pharmacokinetics of Thyroxine Absorption. Thyroxine sodium is erratically but sufficiently absorbed through GIT after its oral administration. Around 50 - 75% of thyroxine sodium is absorbed. Absorption of thyroxine sodium is carried out in jejunum and ileum, and duodenum. Empty stomach or fasting condition will enhance the absorption. As soon as therapy starts, it displays a slow onset of action with peak of therapeutic consequence procured between 3-4 weeks. It displays extended period of action happening between 1-3 weeks, even after the drug is discontinued. Distribution. Thyroxine sodium endure enterohepatic circulation. Once in the circulation, it binds to protein, chiefly to thyroxine binding globulin (TBG) and to some degree with thyroxine binding prealbumin (TBPA) or to albumin. It is circulated with greater concentration in the liver and kidneys as compared to other body tissues. It is also found to be present in breast milk. Metabolism & Excretion. Thyroxine sodium has a plasma half-life in euthyroidism of 6-7 days. In case of hypothyroidism, there is an extended half-life for 9 - 10 days. On the other hand there is a decrease in half-life to 3-4 days in case of hyperthyroidism. Metabolism occurs in liver and kidney from thyroxine to tri-iodothyronine. 40% of thyroxine sodium metabolism results in stationary reverse tri-iodothyronine. This is followed by deiodination to dormant metabolites. It is estimated that 85% of the metabolised thyroxine sodium gets deiodinated. Further, Thyroxine endures enterohepatic recycling and is eliminated in faeces (Davidson, 2000; Katzung, 2009). Pharmacokinetics of Paracetamol Paracetamol is an efficient analgesic as well as antipyretic and does not show any anti-inflammatory effects. It is therefore recommended to patients where salicylates and other nonsteroidal anti-inflammatory medicines are contraindicated. Absorption & Distribution: Oral administration leads to complete absorption in small intestine and displays peak in 10- 60 minutes. Its distribution is homogeneous with capacity of 1 - 1.2l/kg. It has the potential to cross the placenta and is also present in breast milk. It does not display plasma protein binding at the therapeutic levels but it is enhanced with augmented levels. Metabolism: Hepatic metabolism is observed due to microsomal enzymes. Adults, have therapeutic doses conjugated with glucuronide (45 to 55%) or sulfate (20 to 30%). Around 20% is metabolised to catechol through oxidation. Excretion: Paracetamol is eliminated in urine as glucuronide and sulfate conjugates. 5% is eliminated in urine in 24 hrs after ingestion. Excretion half-life differ from 1-3 hrs. Intake of food further holdup paracetamol absorption (Katzung, 2009). Pharmacokinetics of Codeine: Codeine displays its analgesic effect as it is converted to morphine. It shows its effect by binding to the central nervous system and modifies procedures distressing insight to pain and the poignant rejoinder of pain. An amalgamation of paracetamol, codeine and doxylamine augments analgesic effect. Absorption: Through GIT without any intervention with paracetamol absorption. Metabolism: Through O and N-demethylation in liver converted to morphine and norcodeine and other metabolites together with normorphine and hydrocodone. The active metabolite is Morphine. Excretion: Codeine as well as its metabolites are eliminated by kidneys chiefly with glucuronic acid. Elimination completes in 24 hours. It is reported that plasma half-life is 3- 4 hours. It is effective for patients displaying poor metabolism through CYP2D6 (Katzung, 2009). References: Davidson, M; Marwah, A; Sawchuk, RJ; Maki, K; Marwah, P; Weeks, C; Lardy, H. 2000. Safety and pharmacokinetic study with escalating doses of 3-acetyl-7-oxo-dehydroepiandrosterone in healthy male volunteers. Clin Invest Med, 23(5), 300-10. Howland, RD; Mycek, MJ. 2006. Pharmacology: Lippincotts Illustrated Reviews. 3rd Edition, Lippincott William & Wilkins. Huber, R; Hartmann, M; Bliesath, H; Lühmann, R; Steinijans, VW; Zech, K. 1996. Pharmacokinetics of pantoprazole in man. Int J Clin Pharmacol Ther, 34(5), 185-94. Katzung, BG; Masters SB; Trevor, AJ. 2009. Basics and Clinical Pharmacology. 11th Edition,Tata McGraw-Hill Marino, MR; Vachharajani, NN. 2001. Drug interaction with Irbesartan. Clinical Pharmacokinetics, 48(8), 605-614. Verzijl, JM; Kamphuis, ThJ; Rensma, PL; van Roon, EN. 2000. Clearance of an oral delayed‐release mesalazine preparation (Salofalk®) by haemodialysis—pharmacokinetic profile of mesalazine related to the effects of dialysis. Nephrol. Dial. Transplant, 15(5), 736-738. Wan, SH; Koda, RT;Maronde, RF. 1979. Pharmacokinetics, pharmacology of Atenolol and effect of renal disease. Br J Clin Pharmacol, 7(6), 569-574. Read More