Quinidine(CAS No. 56-54-2)

Quinidine C20H24N2O2 (cas 56-54-2) Molecular Structure

56-54-2 Structure

Identification and Related Records

【Name】
Quinidine
【CAS Registry number】
56-54-2
【Synonyms】
Quinidine free base
(+)-Quindine
【EINECS(EC#)】
200-279-0
【Molecular Formula】
C20H24N2O2 (Products with the same molecular formula)
【Molecular Weight】
324.42
【Inchi】
InChI=1/C20H24N2O2/c1-3-13-12-22-9-7-14(13)10-19(22)20(23)16-6-8-21-18-5-4-15(24-2)11-17(16)18/h3-6,8,11,13-14,19-20,23H,1,7,9-10,12H2,2H3/t13-,14?,19+,20-/m0/s1
【Canonical SMILES】
COC1=CC2=C(C=CN=C2C=C1)C(C3CC4CCN3CC4C=C)O
【Isomers smiles】
COC1=CC2=C(C=CN=C2C=C1)[C@@H]([C@H]3C[C@@H]4CCN3C[C@@H]4C=C)O
【MOL File】
56-54-2.mol

Chemical and Physical Properties

【Appearance】
white to light yellow crystal powde
【Density】
0.05 g/100 mL (20ºC)
【Melting Point】
170-175℃
【Boiling Point】
495.9 °C at 760 mmHg
【Flash Point】
253.7 °C
【Alpha】
256 º (C=1, ETOH)
【Water】
0.05 g/100 mL (20℃)
【Solubilities】
0.05 g/100 mL (20ºC) in water
【Color/Form】
Occurs as fine, needle-like, white crystals which frequently cohere in masses or as a fine, white powder.
【Stability】
Stable. Incompatible with strong oxidizing agents.
【Storage temp】
Keep containers tightly closed. Store protected from light. Store in a cool, dry area away from incompatible substances.
【Spectral properties】
IR: 8162 (Sadtler Research Laboratories IR Grating Collection)
UV: 11429 (Sadtler Research Laboratories Spectral Collection)
【Computed Properties】
Molecular Weight:324.41676 [g/mol]
Molecular Formula:C20H24N2O2
XLogP3:2.9
H-Bond Donor:1
H-Bond Acceptor:4
Rotatable Bond Count:4
Exact Mass:324.183778
MonoIsotopic Mass:324.183778
Topological Polar Surface Area:45.6
Heavy Atom Count:24
Formal Charge:0
Complexity:457
Isotope Atom Count:0
Defined Atom Stereocenter Count:4
Undefined Atom Stereocenter Count:0
Defined Bond Stereocenter Count:0
Undefined Bond Stereocenter Count:0
Covalently-Bonded Unit Count:1
Feature 3D Acceptor Count:3
Feature 3D Donor Count:1
Feature 3D Cation Count:1
Feature 3D Hydrophobe Count:1
Feature 3D Ring Count:3
Effective Rotor Count:5.2
Conformer Sampling RMSD:0.8
CID Conformer Count:4

Safety and Handling

【Hazard Codes】
Xn:Harmful;
【Risk Statements】
R22
【Safety Statements 】
S22;S36
【HazardClass】
6.1(b)
【PackingGroup 】
III
【Sensitive】
Light Sensitive
【Skin, Eye, and Respiratory Irritations】
Skin irritant.
【Cleanup Methods】
If a spill of this chemical occurs, FIRST REMOVE ALL SOURCES OF IGNITION, then you should dampen the solid spill material with acetone and transfer the dampened material to a suitable container. Use absorbent paper dampened with acetone to pick up any remaining material. Seal your contaminated clothing and the absorbent paper in a vapor-tight plastic bag for disposal Solvent wash all contaminated surfaces with acetone followed by washing with a soap and water solution. Do not reenter the comtaminated area until safty officer has verified that the area has been properly cleaned.
【Transport】
UN 2811
【Fire Potential】
SLIGHT.
【Formulations/Preparations】
QUINIDINE SULFATE CONTAINS 82% OF QUINIDINE BASE BY WEIGHT ... .
QUINIDINE SULFATE AVAILABLE ... CAPSULES, CONTAIN 100 ... MG OF THE DRUG; TABLETS OF QUINIDINE POLYGALACTURONATE CONTAIN 275 MG, EQUIVALENT TO 200 MG OF QUINIDINE SULFATE. PREPN FOR SLOW ABSORPTION ARE ALSO AVAILABLE AS 300 MG EXTENDED RELEASE TABLET OF QUINIDINE SULFATE & A 324 MG TABLET OF GLUCONATE. QUINIDINE SULFATE IS ALSO AVAILABLE AS AN INJECTION IN 1 ML AMPULE CONTAINING 200 MG/ML. THE NECESSARY DOSE IS DILUTED TO 800 MG/50 ML IN 5% GLUCOSE SOLUTION AND IS INJECTED AT THE RATE OF 16 MG/MIN, WITH CONTINUOUS OBSERVATION OF THE PATIENT & OF THE ECG.
Oral Tablets extended release 324 mg (equivalent to quinidine 202 mg), Quinaglute Dura-Tabs, Berlex, Quinatime, CMC; 330 mg (equivalent to quinidine 206 mg), Duraquine (with povidone), Warner Chilcott; Parenteral injection, 80 mg (equivalent to quinidine 50 mg) per ml, quinidine gluconate injection (with edetate disodium and phenol). Lilly /Quinidine Gluconate/
Oral Tablets 275 mg (equivalent to quinidine sulfate 200 mg), Cardioquin (with povidone; scored), Purdue Frederick. /Quinidine polygalacturonate/
Oral Tablets, 200 mg, 300 mg, Quinora, Key; Tablets, extended-released, 300 mg, Quinidex Extentabs, Robins /Quinidine Sulfate/
Capsules and tablets 100, 200, and 300 mg. Controlled release tablets, 300 mg. Ampules, 200 mg/ml.
QUINIDINE SULFATE IS AVAILABLE AS TABLETS (100 TO 300 MG) CAPSULES 200, AND 300 MG. 300 MG SUBSTAINED RELEASE TABLETS (QUINIDEX) ARE AVAILABLE, AS IS AN INJECTION (200 MG/ML). PREPARATIONS OF THE GLUCONATE AND POLYGALACTURONATE SALTS ARE ALSO MARKETED.
【Exposure Standards and Regulations】
Manufacturers, packers, and distributors of drug and drug products for human use are responsible for complying with the labeling, certification, and usage requirements as prescribed by the Federal Food, Drug, and Cosmetic Act, as amended (secs 201-902, 52 Stat. 1040 et seq., as amended; 21 U.S.C. 321-392).
The Approved Drug Products with Therapeutic Equivalence Evaluations List identifies currently marketed prescription drug products, incl quinidine sulfate, approved on the basis of safety and effectiveness by FDA under sections 505 and 507 of the Federal Food, Drug, and Cosmetic Act.
【Protective Equipment and Clothing】
Skin irritant.
【Octanol/Water Partition Coefficient】
log Kow = 2.88
【Disposal Methods】
SRP: The most favorable course of action is to use an alternative chemical product with less inherent propensity for occupational exposure or environmental contamination. Recycle any unused portion of the material for its approved use or return it to the manufacturer or supplier. Ultimate disposal of the chemical must consider: the material's impact on air quality; potential migration in soil or water; effects on animal, aquatic, and plant life; and conformance with environmental and public health regulations.

Use and Manufacturing

【Use and Manufacturing】
Methods of Manufacturing

EXTRACTION FROM CINCHONA BARK WITH SLAKED LIME, FOLLOWED BY AQ SODIUM HYDROXIDE OR CARBONATE TREATMENT, EXTRACTION INTO HOT MINERAL OIL, SEPN USING SULFURIC ACID, THEN DIL SODIUM HYDROXIDE, & PURIFICATION BY RECRYSTALLIZATION
Finely ground cinchona bark mixed with lime is extracted with hot, high-boiling paraffin oil. The solution is filtered, shaken with dilute sulfuric acid, and the latter neutralized while still hot with sodium carbonate; on cooling, quinine sulfate crystallized out. The sulfate is then treated with ammonia, the alkaloid being obtained.
U.S. Exports

(1972) ND
(1975) ND
U.S. Imports

(1972) 4.8X10+7 GRAMS
(1975) 4.87X10+7 GRAMS
U.S. Production

(1972) PROBABLY GREATER THAN 4.54X10+5 GRAMS
(1975) PROBABLY GREATER THAN 4.54X10+5 GRAMS
Consumption Patterns

100% AS A CARDIAC DEPRESSANT TO INHIBIT AURICULAR FIBRILLATION (1975)
【Usage】
A dextrorotatory stereoisomer of Quinine. Antiarrhythmic (class IA). Antimalarial

Biomedical Effects and Toxicity

【Pharmacological Action】
- Drugs that bind to but do not activate alpha-adrenergic receptors thereby blocking the actions of endogenous or exogenous adrenergic agonists. Adrenergic alpha-antagonists are used in the treatment of hypertension, vasospasm, peripheral vascular disease, shock, and pheochromocytoma.
- Agents used for the treatment or prevention of cardiac arrhythmias. They may affect the polarization-repolarization phase of the action potential, its excitability or refractoriness, or impulse conduction or membrane responsiveness within cardiac fibers. Anti-arrhythmia agents are often classed into four main groups according to their mechanism of action: sodium channel blockade, beta-adrenergic blockade, repolarization prolongation, or calcium channel blockade.
- Agents used in the treatment of malaria. They are usually classified on the basis of their action against plasmodia at different stages in their life cycle in the human. (From AMA, Drug Evaluations Annual, 1992, p1585)
- Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction.
- Drugs that bind to but do not activate MUSCARINIC RECEPTORS, thereby blocking the actions of endogenous ACETYLCHOLINE or exogenous agonists. Muscarinic antagonists have widespread effects including actions on the iris and ciliary muscle of the eye, the heart and blood vessels, secretions of the respiratory tract, GI system, and salivary glands, GI motility, urinary bladder tone, and the central nervous system.
【Therapeutic Uses】
Adrenergic alpha-Antagonists; Anti-Arrhythmia Agents; Antimalarials; Enzyme Inhibitors; Muscarinic Antagonists
Quinidine is indicated in the treatment of recurrent, documented, life-threatening ventricular arrhythmias, such as sustained ventricular tachycardia. Quinidine should not be used to treat ventricular arrhythmias of lesser severity, such as asymptomatic ventricular premature contractions. /Included in US product labeling/
Quinidine is indicated in the treatment of symptomatic atrial fibrillation or flutter in patients whose symptoms are not controlled by measures to reduce the rate of ventricular response. /US Product Labeling/
Chronic quinidine treatment is indicated for some patients at high risk for symptomatic atrial fibrillation pr flutter, such as those who have had previous episodes taht are so frequent and poorly tolerated as to outweigh the risk of porphylactic therapy with quinidine. /US Product Labeling/
Intravenous quinidine is indicated in the treatment of life-threatening Plasmodium falciparum malaria. /US Product Labeling/
Analgesics, Non-Narcotic; Antimalarials; Muscle Relaxants, Central
... 2 VALID THERAPEUTIC APPLICATIONS: FOR TREATMENT OF MALARIA & RELIEF OF NOCTURNAL LEG CRAMPS.
ACTS PRIMARILY AS A BLOOD SCHIZONTOCIDE; IT HAS LITTLE EFFECT ON SPOROZOITES OR PREERYTHROCYTIC TISSUE FORMS. ... IS GAMETOCYTOCIDAL FOR PLASMODIUM VIVAX & MALARIAE BUT NOT FOR PLASMODIUM FALCIPARUM.
/QUININE/ IS TOXIC TO MANY BACTERIA & OTHER UNICELLULAR ORGANISMS SUCH AS TRYPANOSOMES, INFUSORIA, YEAST, PLASMODIA, & SPERMATOZOA. ... MOLDS GROW FREELY IN QUININE SOLN; ONLY HIGH CONCN OF DRUG INJURIOUS TO SPERM CELLS & BACTERIA.
MEDICATION (VET): BITTER STOMACHIC, ANALGESIC, ANTIPYRETIC.
PROPOSED DOSAGE BASED ON PHARMACOKINETIC PARAMETERS & PREDICTED AVG BLOOD LEVELS IN SUPPRESSIVE TREATMENT & PREDICTED PEAK BLOOD LEVELS IN THERAPEUTIC TREATMENT. [RITSCHEL WA ET AL; INT J CLIN PHARMACOL BIOPHARM 16 (SEPT): 395-401 (1978)]
【Biomedical Effects and Toxicity】
ABOUT 90% OF QUINIDINE IN PLASMA IS BOUND TO PLASMA PROTEINS (ALPHA/ACID GLYCOPROTEIN AND ALBUMIN) THE DRUG ENTERS ERYTHROCYTES & ... BINDS TO HEMOGLOBIN; AT STEADY STATE, CONCN OF QUINIDINE IN PLASMA & ERYTHROCYTES ARE APPROXIMATELY EQUAL. QUINIDINE ACCUMULATES RAPIDLY IN MOST TISSUES EXCEPT BRAIN, & ... VOL OF DISTRIBUTION IS 2-3 L/KG. /QUINIDINE/
METABOLITES AND SOME OF THE PARENT DRUG (20%) ARE EXCRETED IN URINE; ELIMINATION HALF-TIME IS ABOUT 6 HR. /QUINIDINE/
LIVER METABOLISM & RENAL EXCRETION ARE THE MAIN ROUTES OF ELIMINATION. ENTEROHEPATIC CIRCULATION WOULD NOT SIGNIFICANTLY ALTER ABSORPTION KINETICS AS REFLECTED BY BLOOD CONCENTRATION. [KOSKAS J ET AL; J PHARM BELG 36 (3): 193 (1981)] PubMed Abstract
PEAK PLASMA CONCN OF 0.29 UG/ML OF QUINIDINE WERE MEASURED @ 4 HR AFTER ADMIN OF SUSTAINED RELEASE CAPSULE (250 MG QUINIDINE BISULFATE) AND DECLINED STEADILY DURING THE NEXT 8 HR, WHILE AFTER ADMIN OF SUSTAINED RELEASE TABLET (300 MG QUINIDINE SULFATE) THEY WERE FAIRLY EVEN DURING 2-10 HR AFTER DOSING. PLASMA CONCENTRATIONS WERE HIGHER AT LATER TIMES FOR THE CAPSULE THAN FOR THE TABLET. THE BIOAVAILABILITY OF QUINIDINE FROM THE CAPSULES DURING 12 HR WAS 184% COMPARED TO THE TABLET. MEAN QUINIDINE PLASMA CONCN WERE SIGNIFICANTLY GREATER @ 3, 4, 6, 8, & 10 HR AFTER ADMIN OF THE CAPSULE THAN AFTER THE TABLET.
DURING MAINTENANCE THERAPY QUINIDINE WILL REACH A STEADY STATE /USUAL ORAL DOSE IS 200-300 MG THREE TO FOUR TIMES A DAY/ WITHIN ABOUT 24 HR AND ITS CONCENTRATIONS IN PLASMA WILL FLUCTUATE LESS THAN 50% BETWEEN DOSES. BECAUSE OF THE LARGE INTERINDIVIDUAL VARIATION ... AND OTHER CAUSES OF VARIABILITY, IT IS WISE TO ... MEASURE THE PLASMA CONCENTRAION OF THE DRUG AT STEADY STATE.
WHEN ADMIN ON AN EMPTY STOMACH, ABSORPTION /OF QUINIDINE SULFATE/ IS RELATIVELY RAPID, WITH PEAK SERUM QUINIDINE LEVELS REACHED WITHIN 3 HR OF THE DOSE. ABSORPTION IS APPROXIMATELY 80% COMPLETE. BECAUSE OF ITS RAPID ABSORPTION, MAINTENANCE DOSES OF QUINIDINE SULFATE GENERALLY MUST BE GIVEN EVERY 6 TO 8 HR TO PROVIDE ACCEPTABLE INTERDOSE FLUCTUATION OF SERUM CONCENTRATIONS.
THREE QUINIDINE FORMULATIONS CONTAINING 0.33 G OF QUINIDINE BASE EACH, WERE TAKEN BY 6 HEALTHY MALES EVERY 12 HR FOR 96 HR. RAPIDLY DISSOLVING QUINIDINE BISULFATE TABLETS PRODUCE A MEAN SERUM LEVEL OF 1.8 MG/L, LONG ACTING QUINIDINE DURULES (SUSTAINED RELEASE BISULFATE) PRODUCE A LEVEL 23% LOWER; LONGACOR (QUINIDINE ARABOGALACTAN SULFATE) 46% LOWER. SERUM LEVELS ATTAINED WITH QUINIDINE BISULFATE ARE MORE VARIABLE THAN THOSE PRODUCED BY EITHER LONG LASTING QUINIDINE DURULES OR LONGACOR. THERAPEUTIC SERUM LEVEL CAN BE MAINTAINED WITH NO TOXIC EFFECT BY 3 TABLETS OF LONG ACTING QUINIDINE DURULES AND 4 TABLETS OF LONGACOR (QUINIDINE ARA). [HENNING R, NYBERG G; EUR J CLIN PHARMACOL 6 (4): 239 (1973)] PubMed Abstract
SEVEN HEALTHY ADULT COWS WEIGHING BETWEEN 550 & 750 KG WERE ADMIN QUINIDINE GLUCONATE (5 MG/KG) IV AND QUINIDINE SULFATE (15.84 MG/KG) ORALLY TO DETERMINE PHARMACOKINETIC VALUES. THE APPARENT VOLUME OF DISTRIBUTION WAS 3.80 L/KG. TOTAL BODY CLEARANCE WAS 19.0 ML/MIN/KG AND PLASMA HALF-LIFE WAS 2.25 HR. THE SYSTEMIC AVAILABILITY OF QUINIDINE SULFATE AFTER ORAL ADMIN OF A 20 MG/KG DOSE WAS 23.3%. THE MEAN PEAK PLASMA CONCN REACHED IN 7 COWS AFTER ORAL ADMIN OF QUINIDINE SULFATE WAS 0.26 UG/ML. [MCGUIRK SM ET AL; AM J VET RES 42 (9): 1482 (1981)] PubMed Abstract
PHARMACOKINETICS OF QUINIDINE SULFATE ORALLY WAS DETERMINED IN HORSES. THE SYSTEMIC AVAILABILITY OF QUINIDINE SULFATE AFTER ORAL ADMIN OF A 10 MG/KG DOSE WAS 48.5%. [MCGUIRK SM ET AL; AM J VET RES 42 (6): 938 (1981)] PubMed Abstract
THE PHARMACOKINETICS OF QUINIDINE (GIVEN AS THE SULFATE SALT) WAS STUDIED FOLLOWING EQUIMOLAR IV DOSES IN RABBITS. TWO COMPARTMENT OPEN MODEL PHARMACOKINETICS WAS OBSERVED. [UEDA CT, NICKOLS JG; J PHARM SCI 69 (DEC): 1400 (1980)] PubMed Abstract
A GRAVID PATIENT WAS GIVEN QUINIDINE FOR IDIOPATHIC VENTRICULAR TACHYCARDIA. AT DELIVERY, MATERNAL & NEONATAL QUINIDINE LEVELS WERE EQUIVALENT WHILE THE LEVEL IN THE AMNIOTIC FLUID WAS SIGNIFICANTLY ELEVATED. [HILL LM, MALKASIAN GD; OBSTET GYNECOL 54: 366 (1979)] PubMed Abstract
THERAPEUTIC SERUMLEVELS OF 2-5 MG QUINIDINE/L WERE ACHIEVED IN VOLUNTEERS AND PATIENTS WITH CARDIAC ARRHYTHMIA AFTER ADMIN OF QUINIDINE MONOSULFATE TABLETS (200 MG/TABLET, 2 TABLETS 3 TIMES/DAY) OR OF PROLONGED ACTING QUINIDINE BISULFATE TABLETS (EQUIV DOSE/TABLET, 3 TABLETS 2 TIMES/DAY). THE PROLONGED ACTING PREPN PROVIDED A MORE STABLE SERUM LEVEL AND LESS GI COMPLAINTS.
Quinidine salts are almost completely absorbed from the GI tract. The amount of drug which reaches the circulation after oral administration of quinidine depends on the amount of drug metabolized on the first pass through the liver. The polygalacturonate derivative is slowly dissociated in the GI tract and absorbed as free quinidine. Extended release formulations of quinidine gluconate and quinidine sulfate are absorbed more slowly than are conventional capules (no longer commercially available in US) and tablets of the sulfate salt. Plasma quinidine concentrations are generally higher and appear earlier when the drug is administered on an empty stomach than when the drug is given after meals. Concomitant administration of antacids may delay oral absorption of quinidine. In patients with congestive heart failure, the rate and extent of quinidine absorption is reduced but these patients have higher plasma concentrations of quinidine due to a decreased volume of distribution.
Plasma quinidine concentrations are quite variable among individuals. In healthy fasting individuals, mean peak plasma quinidine concentrations of 0.43-1.14 ug/ml are attained 1-2 hr following oral administration of a single 200 mg dose of quinidine sulfate. Plasma concentrations of quinidine generally reach steady state after oral administration of 4-6 doses (200-300 mg) of quinidine sulfate at 2 hr intervals. If higher plasma concentrations are necessary after this time, the size of the individual dose must be increased. In one study in healthy individuals, plasma concentrations of the drug ranged from 0.4-1 ug/ml during the 4 hr after im administration of 321 mg of quinidine gluconate. Immediately following iv infusion over 4 hr of a single 24 mg/kg dose of quinidine gluconate in patients with Plasmodium faciparum malaria, plasma quinidine concentrations average 9.4 ug/ml.
Effective reduction of ventricular premature contractions has been reported with plasma quinidine concentrations less than 1 ug/ml. After oral administration of 400-600 mg of quinidine sulfate, the onset of action usually occurs in 1-3 hr and therapeutic cardiovascular effects persist for 6-8 hr.
Quinidine is rapidly distributed into all body tissues except the brain. The volume of distribution of the drug reportedly averages 2 l/kg in healthy adults and 0.9-1.8 l/kg in patients with malaria. Quinidine is concentrated in heart, liver, kidneys, and skeletal muscle. Quinidine also is distributed into erythrocytes, where it is bound to hemoglobin. In one study in patients with cerebral Plasmodium falciparum malaria who received iv quinidine gluconate, CSF concentrations of quinidine were 7-17% of plasma concentrations.
Quinidine crosses the placenta and is distributed into milk.
Approximately 80% of quinidine is bound to plasma albumin at therapeutic plasma concentrations; this binding is decreased in the presence of hypoalbuminemia from various causes, including cirrhosis.
The rate of renal excretion of quinidine increases when the pH of urine is 6 or less; the rate of excretion decreases and plasma quinidine concentrations increase when urine is alkaline. Less than 5% of the orally administratered drug is excreted in feces. Small amounts of quinidine are removed by hemodialysis; the drug is not removed by peritoneal dialysis.
The sulfate salt /of quinidine/ is rapidly absorbed in 60 to 90 minutes.
The pharmacokinetics of quinine and its diastereoisomer quinidine has been investigated in normal and febrile rats. Endotoxin induced fever in rats resulted in an increased quinine clearance (4.49 + or - 1.45 vs 1.38 + or - 0.65 l/hr/kg, pPubMed Abstract
To account for the variability in quinidine pharmacokinetic parameters, blood samples from 139 adult male hospitalized patients (ages 42-92 yr) who were receiving either oral quinidine sulfate or quinidine gluconate were assayed and analyzed using NONMEM to develop a pharmacokinetic and statistical model for quinidine. Results indicated that oral quinidine clearance decreased with age, severe congestive heart failure, and renal disease, and increased in patients with a history of alcohol abuse. However, when alpha1 acid glycoprotein was measured and incorporated into the model, the only important covariates of clearance were the alpha1 acid glycoprotein measurements and the presence of renal dysfunction. It was concluded that quinidine elimination is dependent on the free concentration of drug in plasma. /Quinidine/ [Verme CN et al; Clin Pharmacokinet 22 (6): 468-80 (1992)] PubMed Abstract
The disposition of the diastereoisomers quinine and quinidine was investigated in 5 near term pregnant ewes given 5.12 and 8.85 mg/kg iv boluses followed by 2.71 and 5.59 mg/kg/hr of quinidine and quinine, respectively, in random order. Systemic clearance of quinine tended to be greater than that of quinidine. Maternal renal clearance exhibited no stereoselectivity and represented PubMed Abstract
The population pharmacokinetics of quinidine were determined based on 260 serum drug concentration measurements in 60 patients (aged 28-82 yr) with arrhythmias who received treatment with oral quinidine sulfate (Chinidin sulfuricum) or quinidine bisulfate (Kinidin Durules). Quinidine kinetics were best described bya 2 compartment model with zero order absorption. The pharmacokinetics were influenced by severe heart or liver failure and renal function impairment. No effect was found for mild or moderate heart failure, age, body wt or for coadministration of nifedipine. Nonrenal drug clearance of the drug in patients without severe heart and liver failure was 12.6 l/hr, compared with 6.8 l/hr in those with severe heart or liver failure. Volume of distribution of the central compartment was 161 l. The maximum serum drug concentration was achieved 1.4 hr after administration of quinidine sulfate and 6 hr after administration of the bisulfate. The results were validated by the reliable prediction of the serum drug levels in a separate group of 30 patients. Using computer simulations, on a priority dosing regimen was derived to maximize the proportion of patients having quinidine serum levels within the recommended range of 2-5 mg/l. /Quinidine/ [Fattinger K et al; Br J Clin Pharmacol 31 (Mar): 279-86 (1991)] PubMed Abstract

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