PHA 5128 CASE STUDY 5 (Digoxin, Cyclosporine, and Methotrexate) Spring 2007

Similar documents
PHA Case Studies V (Answers)

PHA Spring First Exam. 8 Aminoglycosides (5 points)

PHA 5128 Spring 2009 First Exam (Version B)

Name: UFID: PHA Exam 2. Spring 2013

Thus, we can group the entire loading dose together as though it was given as a single dose, all administered when the first dose was given.

PHA 5128 Final Exam Spring 2004 Version A. On my honor, I have neither given nor received unauthorized aid in doing this assignment.

PHA 5128 Spring 2000 Final Exam

Carbamazepine has a clearance of L/h/kg for monotherapy. For immediate release carbamazepine, the oral bioavailbility is 0.8

. Although there is a little

Case Study 2 Answers Spring 2006

TDM Lecture 7 5 th Stage. TDM of Digoxin. Uses: Digoxin is usually used in heart failure associated and atrial fibrillation.

PHA Second Exam Fall On my honor, I have neither given nor received unauthorized aid in doing this assignment.

TDM of Digoxin. Use of Digoxin Serum Concentrations to Alter Dosages

PHA5128 Dose Optimization II Case Study 3 Spring 2013

PHA Second Exam. Fall On my honor, I have neither given nor received unauthorized aid in doing this assignment.

PHA Final Exam. Fall On my honor, I have neither given nor received unauthorized aid in doing this assignment.

PHA Final Exam Fall 2006

PHA Final Exam. Fall On my honor, I have neither given nor received unauthorized aid in doing this assignment.

PHA 4120 Second Exam Key Fall On my honor, I have neither given nor received unauthorized aid in doing this assignment.

LD = (Vd x Cp)/F (Vd x Cp)/F MD = (Css x CL x T)/F DR = (Css x (Vm-DR))/Km Css = (F x D)/(CL x T) (Km x DR)/(Vm DR)

PHARMACOKINETICS SMALL GROUP II:

Basic Pharmacokinetic Principles Stephen P. Roush, Pharm.D. Clinical Coordinator, Department of Pharmacy

TDM of Aminoglycoside Antibiotics

CLINICAL PHARMACOKINETICS INDEPENDENT LEARNING MODULE

PHA5128 Dose Optimization II Case Study I Spring 2013

1. If the MTC is 100 ng/ml and the MEC is 0.12 ng/ml, which of the following dosing regimen(s) are in the therapeutic window?

A Computer-based Pharmacokinetic Implementation for Digoxin Therapeutic Monitoring in Pediatric Patients

PHA Second Exam. Fall On my honor, I have neither given nor received unauthorized aid in doing this assignment.

PHA 5127 FINAL EXAM FALL On my honor, I have neither given nor received unauthorized aid in doing this assignment.

PHA Final Exam Fall 2001

General Principles of Pharmacology and Toxicology

TDM. Measurement techniques used to determine cyclosporine level include:

SHC Vancomycin Dosing Guide

PHA 5128 Case Study 4 (Answers) Total Cp = Unbound Cp/fu.

Policy: Created: 2/11/2015; Approved: Adult Pharmacokinetic Dosing and Monitoring- Vancomycin Dosing

Pharmacokinetics Overview

Multiple IV Bolus Dose Administration

Drug Dosing in Renal Insufficiency. Coralie Therese D. Dimacali, MD College of Medicine University of the Philippines Manila

Each tablet contains:

pharmacy, we need to see how clinical pharmacokinetics fits into the pharmaceutical care process.

Section 5.2: Pharmacokinetic properties

PHAR 7632 Chapter 16

Doses Target Concentration Intervention

Myrna Y. Munar, Pharm.D., BCPS

New drugs necessity for therapeutic drug monitoring

Basic Concepts of TDM

AMINOGLYCOSIDES TDM D O N E B Y

Learning Outcomes. Overall Picture. Part 1 Overview of Key Concepts of Clinical Pharmacokine2cs 4/23/14. A- Awaisu- A- Nader- CPPD

Research & Reviews: Journal of Hospital and Clinical Pharmacy

PHA First Exam Fall 2003

General Principles of Pharmacology and Toxicology

BASIC PHARMACOKINETICS

Assessing Renal Function: What you Didn t Know You Didn t Know

USES OF PHARMACOKINETICS

Aminoglycosides. Uses: Treatment of serious gram-negative systemic infections and some grampositive

Tamer Barakat. Abdul Aziz ALShamali. Abdul Aziz ALShamali

Rational Dose Prediction. Pharmacology. φαρμακον. What does this mean? pharmakon. Medicine Poison Magic Spell

Click to edit Master title style

PHA First Exam. Fall 2004

ADME Review. Dr. Joe Ritter Associate Professor of Pharmacology

Chapter-V Drug use in renal and hepatic disorders. BY Prof. C.Ramasamy, Head, Dept of Pharmacy Practice SRM College of Pharmacy, SRM University

OMCJH.CHEM.COLL.INF.1001 Therapeutic Drug Monitoring Guidelines

The general Concepts of Pharmacokinetics

2015 Updates in Therapeutics: The Pharmacotherapy Preparatory Review & Recertification Course Pharmacokinetics: A Refresher Curtis L.

Career Corner: Pharmaceutical Calculations for Technicians. Ashlee Mattingly, PharmD, BCPS

Effect of Multiple-Dose Ketoconazole and the Effect of Multiple-Dose Rifampin on Pharmacokinetics (PK) of the HCV NS3 Protease Inhibitor Asunaprevir

PHARMACOKINETICS SMALL GROUP I:

PHA Second Exam. Fall On my honor, I have neither given nor received unauthorized aid in doing this assignment.

Use ideal body weight (IBW) unless actual body weight is less. Use the following equation to calculate IBW:

Edoxaban. Direct Xa inhibitor Direct thrombin inhibitor Direct Xa inhibitor Direct Xa inhibitor

PRUCAPLA Tablets (Prucalopride)

Evaluation and Quantitative Prediction of Renal Transporter-Mediated Drug-Drug Interactions. Bo Feng, Ph.D. DDI 2017 June 19-21, 2017

MEDICATION MONITORING: Pharmacist-Managed Intravenous (IV) Vancomycin Protocol

Lung Pathway Group Afatinib in Non-Small Cell Lung Cancer (NSCLC)

Selected Properties of Ledipasvir

Pharmacokinetics in Drug Development. Edward P. Acosta, PharmD Professor & Director Division of Clinical Pharmacology Director, CCC PK/PD Core

Tvaptan. Tvaptan Tablets 15 mg. Label claim: Each uncoated tablet contains: Tolvaptan mg. Colour: Brilliant blue FCF. Tvaptan Tablets 30 mg

Adjusting phenytoin dosage in complex patients: how to win friends and influence patient outcomes

Clinical Toxicology Toxicity of Digitalis Glycosides 5 th Year (Lab 3)

Clinical Study Synopsis for Public Disclosure

Pharmacokinetic parameters: Halflife

Appendix IV - Prescribing Guidance for Apixaban

1 Acute Lymphoblastic Leukaemia

Pharmacokinetics Applied to the Treatment of Asthma

Selected Properties of Daclatasvir

Clinical Pharmacokinetics. Therapeutic Drug Monitoring of Phenytoin

NCCP Chemotherapy Protocol. Afatinib Monotherapy

A prospective study of the clarithromycin digoxin interaction in elderly patients

Understand the physiological determinants of extent and rate of absorption

Pharmacokinetics PCTH 325. Dr. Shabbits September 12, C t = C 0 e -kt. Learning Objectives

NCCP Chemotherapy Regimen. Afatinib Therapy

Pharmacokinetics for Physicians. Assoc Prof. Noel E. Cranswick Clinical Pharmacologist Royal Children s Hospital Melbourne

NOAC Prescribing in Patients with Non-Valvular Atrial Fibrillation: Frequently Asked Questions

Effects of Renal Disease on Pharmacokinetics

Nibal R. Chamoun, Pharm.D., BCPS Clinical Assistant Professor of Pharmacy Practice at the Lebanese American University Clinical Pharmacy Coordinator

Full title of guideline INTRAVENOUS VANCOMYCIN PRESCRIBING AND MONITORING GUIDELINE FOR ADULT PATIENTS. control

DIAGNOSIS AND MANAGEMENT OF DIURETIC RESISTANCE. Jules B. Puschett, M.D.

Recommended dosing for pediatric patients (6 months to 12 years of age) 1. Dose based on lopinavir component* 1.25 ml ml

Comparative Study of Different Digoxin Treatment Regimens in Egyptian Hospitals. For Partial Fulfillment of Master Degree in Pharmaceutical Sciences

Transcription:

PHA 5128 CASE STUDY 5 (Digoxin, Cyclosporine, and Methotrexate) Spring 2007 1. L.J., a 30 year old male, was diagnosed congestive heart failure (CHF). He is 5'9" tall and weights 80 kg. He was given Furosemide to control CHF symptoms. After a couple of days, his physician found that the diuretic therapy cannot control L.J. s CHF, and L.J. also suffers cardiac arrhythmia. The physician decided to give L.J. Lanoxin (Digoxin) tablets and Isoptin (Verapamil) tablets. In order to achieve the therapeutic concentration of Lanoxin (1.5 ng/ml), what would be a suggested loading and maintenance dose regimen for Digoxin? (L.J. s serum creatinine concentration is: 1.4 mg/dl) (Tablets for Digoxin 0.5 mg/0.25mg/0.125mg, and assuming Digoxin is rapidly absorbed.) Given information: Male with CHF, 30 yrs, 5'9", 80 kg, C pcreat 1.4mg/dL Bioavailability for Digoxin Tablets: 0.7 earance-factor: 0.75 from verapamil s effect IBW 50kg + 2.3kg ( Height 5') IBW50kg + 2.3 (9) 70.7 kg TBW<1.2 IBW (140 age) weight creat (72) C pcreat (140 30) 80 creat 87.3 (ml/min) (Use TBW for CL Creat ) (72) 1.4 Digoxin 0.33mL / kg / min IBW + 0.9 creat( with CHF) CL0.33 70.7+0.9 87.3101.9 (ml/min) without Verapamil CLCL 0.7576.43 (ml/min) with Verapamil 76.43 ml/min 1440 min/day 1L/1000 ml 110.1 L/day VDigoxin 3.8L / kg IBW + 3. 1 creat Vd3.8 70.7+3.1 87.3539.3 (L) 1.5 ng/ml1.5 ug/l D F To obtain an initial concentration of 1.5 ug/l, Cp0 Vd LD Cp 0 Vd/F (1.5 ug/l)(539.3 L)/0.7 1155.6 ug ~ 1125 ug (2*500ug + 1*125ug) A maintenance dose to provide the same concentration is: MD Cpss τ / F (110.1 L/day)( 1.5 ug/l)(1 day)/0.7 235.9 ug/day ~ 250 ug/day

2. A recent study was preformed to evaluate Ritonavir s effect on Digoxin pharmacokinetics. Six healthy subjects in the treatment group were given Ritonavir for 2-days until steady state of Ritonavir was reached, and the other 6 subjects in the control group were given placebo for 2 days. On day3, all subjects were given a dose of Digoxin of 0.5 mg. Then blood samples were taken based on designed time points. The quantified digoxin concentrations were plotted with time in the following graph. Table I shows the noncompartmental analysis results. (Ritonavir is a HIV protease inhibitor, and also inhibits metabolism enzymes (CYP450), and P-gp in the renal tubule.) State whether the following statement is TRUE or FALSE? And Why? A: Digoxin could be partially eliminated by P-gp mediated renal tubular secretion. B: Ritonavir had a profound impact on Digoxin distribution. C: Digoxin clearance and volume of distribution need to be corrected by some factor when Digoxin and Ritonavir are co-administered and standard equations for Digoxin clearance and volume of distribution. D: Ritonavir and Quinidine have the same effect on the volume of distribution of Digoxin. E: Toxicity is not an issue when Digoxin and Ritonavir are co-administered. A: True, Ritonavir inhibits P-gp in renal tubule, and Digoxin could be also eliminated by P-gp mediated renal tubular secretion as the renal clearance for digoxin decreases when Ritonavir is co-administered and Digoxin is a P-gp substrate.

B: True, Ritonavir increases digoxin volume of distribution dramatically. C: Ture, Base on the graph and table, it is clearly shown that Ritonavir could decrease Digoxin Total clearance, renal clearance, and increase volume of distribution. Ritonavir has great impacts on both elimination and distribution of Digoxin. Thus, standard equation for Digoxin clearance and volume of distribution is not suitable, similar to Quinidine, but Quinidine decreases the volume of distribution of Digoxin. D: False, See C. E: False, Digoxin concentration could exceed its therapeutic window, resulting in toxicity when total clearance of Digoxin decreases.

3. In a clinical study to assess effects of St. John's Wort (Hypericum perforatum) on Tacrolimus Pharmacokinetics, subjects received St. John's wort (300 mg orally three times daily) for 18 days. On day 19, subjects started to receive multiple oral doses of tacrolimus (3 mg Q12h PO). Subject#1, a male, 45 year old, weights 60 kg. On day 30, this subject s peak and trough concentration (before next dose) were measured, which is 10 ng/ml and 3 ng/ml. Is there any impact from the St. John s Wort on Tacrolimus Pharmacokinetics? Why? (assume CL: 0.06 L/h/kg, and Tacrolimus is rapidly released and absorbed into system.) Given information: Male: 45 yr, 60kg Dose: 3 mg Q12h PO (Bioavailability: 0.25) CL: 0.06L/h/kg Vd: 1 L/kg CL0.06L/h/kg 60kg3.6L/h Vdl L/kg 60kg60 L KeCL/Vd3.6/600.06(1/hr) 0.25 3 e C min 0.012mg/L12ng/mL >> 3ng/mL 60 (1- e ) 0.25 3 C max 0.024mg/L24ng/mL>>10ng/mL 60 (1- e ) This indicates that St. John s Wort could decrease drug concentrations due to its induction effect.

4. R.J, a 70 kg male patient (5'6", 45 year old, C pcreat 1.3 mg/dl) received a 30 mg methotrexate loading dose iv followed by a 45 mg/h infusion over 36 hours. At 36 h, leucovorin rescue (10 mg/m 2 q6h ) was started. Make a recommendation how to continue therapy. When do you expect the methotrexate level to fall below 0.1 μm? Given Information: Male, 70kg, 45 yr, 5 6, C pcreat 1.3 mg/dl Dose: 30 mg LD + 45 mg/h IV IBW 50kg + 2.3kg ( Height 5') IBW50kg + 2.3 (6) 63.8 kg TBW<1.2IBW creat (140 age) weight (72) C pcreat (140 45) 70 creat 71.05 (ml/min) (Use TBW for CL Creat ) (72) 1.3 CL1.6 71 113.6(mL/min)6.82(L/hr) R0 C Pss Cpss45/6.826.6(mg/L)6.6/0.45414.5uM t for 0.5 μm: 14.5 ln t 0.5 14.6h at (14.6 + 36) 50. 6h 0.231 t for 0.1 μm: 0.5 ln t 0.1 23.2h at (50.6 + 23.2) 73.8 h 0.0693