Quinine drug data and news

---

Rooting for happiness  May 12, 2006
...“People were sucking willow bark for pain relief 1,000 years ago. Quinine for malaria is another classic, digitalis for the heart. ... - Times Online,

Wilmington man, 2 in Lewes arrested on heroin charges  May 11, 2006
...medicine. Typically heroin is diluted, or "cut," with common household substances such as sugar, flour, quinine or starch. Oldham ... - The News Journal,

MITRAL VALVE PROLAPSE COMMON AND COMMONLY INNOCUOUS  Apr 23, 2006
DEAR DR. DONOHUE: After reading your article on the side effects of quinine, I wonder if I need to worry about drinking tonic water with my scotch. ... - Charlotte Sun-Herald,

Heroin mix tied to dozens of deaths  May 4, 2006
Heroin sold illegally in the USA typically is diluted, or "cut," with common household substances such as sugar, flour, quinine or starch. ... - USA Today

Man's death attributed to overdose of heroin  May 2, 2006
Street heroin is often mixed with sugar, starch, powdered milk, quinine -- or worse -- the National Institute on Drug Abuse says on its Web site. ... - Patriot-News,

Malaysia May Declare Itself Free Of Bird Flu Next Month  Apr 26, 2006
Referring to orchard owners in Perlis throwing away their harvest of the Sala quinine fruit because of a glut allegedly caused by imports of Thai mangoes ... - Bernama,

Take ‘Arinate’ with another drug for Malaria, says govt  May 4, 2006
...to Malaria. Currently government recognizes SP as the first line treatment for Malaria and Quinine as the effective second line. - The Nation, Malawi,

A Gardener's Diary  Apr 30, 2006
The most common genera include the Mussaenda, Ixora, Gardenia, coffee and quinine, and as you can see by this very short list many plants are highly desirable ... - Stabroek News,

Allegra Goodman’s World of Science  May 4, 2006
She would never imbibe -- or if she sipped his enthusiasm on occasion, she carried her own skepticism with her at all times, like quinine.� But when, led by ... - Bookslut,

Stalking the Szechuan Chef who puts the hot in hot pot  May 5, 2006
But despite its eye-catching preparation and medicinal qualities (that bitter flavor comes from quinine!), I've yet to acquire a taste for the stuff. ... - Seattle Times,

Botswana: Malaria Commemoration in Maun  Apr 25, 2006
...this year. Botswana does not use ACT but instead uses Sulphadoxine Pyrimethamine and Quinine because they are still effective. The ... - AllAfrica.com,

History wars surround Kokoda campaign  Apr 25, 2006
The Dutch Antilles they'd taken, which had the - Java had the largest supply of quinine in the world. They'd taken Rabal and bayonetted Australians there. ... - ABC Online,

Scientists find way to cheaper malaria drug  Apr 17, 2006
...treatment has become more difficult in recent years because the parasite that causes malaria has become resistant to drugs such as quinine and chloroquine. ... - Monterey County Herald,

Sachs Stresses Role Of Extreme Poverty  Apr 24, 2006
..."A bad mosquito bite - and your child dies. You get to the clinic and they're out of quinine - and your child dies," Sachs said. - Cornell University The Cornell Daily Sun,

Sierra Leone join to celebrate Africa Malaria Day Today Malaria ...  Apr 25, 2006
ACT)- a combination of Artesunate and Amodiaquine (AS+ AQ), Artemether Lumefantrine (CO-ARTEM) , Artesunate and Amodiaquine, Quinine and Sulphodoxine ... - Awareness Times,

Shoot the messenger  Apr 24, 2006
...to shoot the porter carrying his precious medical box dead if he let it drop into the flood with its precious cargo of whiskey, gin and quinine chaser. ... - Mail & Guardian Online,

What do evolution and climate change have in common?  Apr 17, 2006
Chloroquine, a relative of the quinine present in colonial gin and tonics, has has such widespread use that the evolutionary pressure to develop resistance has ... - Ars Technica,

Natural Wonders: Delicate flying creatures' survival is winter ...  Apr 29, 2006
...from the Cinchona tree, which reduced the fever of malaria, but they didn't know how it worked nor that the bark contained quinine. ... - Enterprise-Record,

Save to Del.icio.us  Apr 23, 2006
...and huts. Quinine is being distributed in large amounts and the surgeons are working like Trojans to aid the distressed. The gloomy ... - International Herald Tribune,

Effects of Drugs and Other Agents on Quinine Pharmacokinetics

Antacids: Antacids containing aluminum and/or magnesium may delay or decrease absorption of quinine. Concomitant administration of these antacids with quinine should be avoided.

Cholestyramine: In 8 healthy volunteers who received quinine sulfate 600 mg with or without 8 grams of cholestyramine resin, no significant difference in quinine pharmacokinetic parameters was seen.

Erythromycin (CYP3A4 inhibitor): Erythromycin was shown to inhibit the metabolism of quinine in vitro using human liver microsomes. Therefore, concomitant administration of erythromycin with quinine sulfate is likely to increase plasma quinine concentrations, and should be avoided.

Grapefruit juice (CYP3A4 inhibitor): In a pharmacokinetic study involving 10 healthy volunteers, the administration of a single 600 mg dose of quinine sulfate with grapefruit juice (full-strength or half-strength) did not significantly alter the pharmacokinetic parameters of quinine. Quinine sulfate may be taken with grapefruit juice.

Histamine H2-receptor blockers (cimetidine, ranitidine): In healthy volunteers who were given a single oral 600 mg dose of quinine sulfate after pretreatment with cimetidine (200 mg three times daily and 400 mg at bedtime for 7 days) or ranitidine (150 mg twice daily for 7 days), the apparent oral clearance of quinine decreased and the mean elimination half- life increased significantly when given with cimetidine but not with ranitidine. Compared to untreated controls, the mean AUC of quinine increased by only 20% with ranitidine and by 42% with cimetidine (p<0.05) without a significant change in mean quinine C_max. When quinine is to be given concomitantly with a histamine H₂ receptor blocker, the use of ranitidine is preferred over cimetidine. Although cimetidine may be used concomitantly with quinine sulfate, patients should be monitored closely for adverse events associated with quinine.

Isoniazid: Isoniazid 300 mg/day pretreatment for 1 week did not significantly alter the pharmacokinetic parameters of quinine. Adjustment of quinine dosage is not necessary when isoniazid is given concomitantly.

Ketoconazole (CYP3A4 inhibitor): In a crossover study, healthy subjects (N=9) who received a single oral dose of quinine hydrochloride (500 mg) concomitantly with ketoconazole (100 mg twice daily for 3 days) had a mean quinine AUC that was higher by 45% and a mean oral clearance of quinine that was 31% lower than after receiving quinine alone. Although no change in the quinine dosage regimen is necessary with concomitant ketoconazole, patients should be monitored closely for adverse reactio ns associated with quinine sulfate.

Oral contraceptives (estrogen, progestin): In 7 healthy females who were using single ingredient progestin or combination estrogen-containing oral contraceptives, the pharmacokinetic parameters of a single 600 mg dose of quinine sulfate were not altered in comparison to those observed in 7 age- matched female control subjects not using oral contraceptives.

Rifampin (CYP3A4 inducer): In patients with uncomplicated P. falciparum malaria who received quinine sulfate 10 mg/kg concomitantly with rifampin 15 mg/kg/day for 7 days (N=29), the median AUC of quinine between days 3 and 7 of therapy was 75% lower as compared to those who received quinine monotherapy. In healthy volunteers (N=9) who received a single oral 600 mg dose of quinine sulfate after 2 weeks of pretreatment with rifampin 600 mg/day, the mean quinine AUC and C max decreased by 85% and 55%, respectively. Therefore the concomitant administration of rifampin with quinine sulfate should be avoided .

Tetracycline: In 8 patients with acute uncomplicated P. falciparum malaria who were treated with oral quinine sulfate (600 mg every 8 hours for 7 days) in combination with oral tetracycline (250 mg every 6 hours for 7 days), the mean plasma quinine concentrations were about two- fold higher than in 8 patients who received quinine monotherapy. Although tetracycline may be concomitantly administered with quinine sulfate, patients should be monitored closely for adverse reactions associated with quinine sulfate.

Troleandomycin (CYP3A4 inhibitor): In a crossover study (N=10), healthy subjects who received a single oral 600 mg dose of quinine sulfate with the macrolide antibiotic, troleandomycin (500 mg every 8 hours) exhibited a 87% higher mean quinine AUC, a 45% lower mean oral clearance of quinine, and a 81% lower formation clearance of the main metabolite, 3-hydroxyquinine, than when quinine was given alone. Therefore, concomitant administration of troleandomycin with quinine sulfate should be avoided.

Urinary alkalizers (acetazolamide, sodium bicarbonate): Urinary alkalinizing agents may increase plasma quinine concentrations.

Effect of Quinine on the Pharmacokinetics of Other Drugs

Results of in vivo and in vitro drug interaction studies suggest that quinine has the potential to inhibit the metabolism of drugs that are substrates of CYP3A4 and CYP2D6, as well as inhibit the biliary excretion of drugs like digoxin.

Anticonvulsants (carbamazepine, phenobarbital, and phenytoin): A single 600 mg oral dose of quinine sulfate increased the mean plasma C max, and AUC_0-24 of single oral doses of carbamazepine (200 mg) and phenobarbital (120 mg) but not phenytoin (200 mg) in 8 healthy subjects. The mean AUC increases of carbamazepine, phenobarbital and phenytoin were 104%, 81% and 4%, respectively; the mean increases in C max were 56%, 53%, and 4%, respectively. Mean urinary recoveries of the three antiepileptics over 24 hours were also profoundly increased by quinine. If concomitant administration with carbamazepine or phenobarbital cannot be avoided, frequent monitoring of anticonvulsant drug concentrations is recommended. Additionally, patients should be monitored closely for adverse reactions associated with these anticonvulsants. Carbamazepine, phe nobarbital, and phenytoin are CYP3A4 inducers and may decrease quinine plasma concentrations if used concurrently with quinine sulfate.

Astemizole (CYP3A4 substrate): Elevated plasma astemizole concentrations were reported in a subject who experienced torsades de pointes after receiving three doses of quinine sulfate for nocturnal leg cramps concomitantly with chronic astemizole 10 mg/day. The concurrent use of quinine with astemizole and other CYP3A4 substrates with QT prolongation potential (e.g., cisapride, terfenadine, halofantrine, pimozide, and quinidine ) should also be avoided

Desipramine (CYP2D6 substrate): Quinine (750 mg/day for 2 days) decreased the metabolism of desipramine in patients who were extensive CYP2D6 metabolizers, but had no effect in patients who were poor CYP2D6 metabolizers. Lower doses (80 mg to 400 mg) of quinine did not significantly affect the pharmacokinetics of other CYP2D6 substrates, namely, debrisoquine, dextromethorphan, and methoxyphenamine. Although clinical drug interaction studies have not been performed, antimalarial doses (greater than or equal to 600 mg) of quinine may inhibit the metabolism of other drugs that are CYP2D6 substrates (e.g., flecainide, debrisoquine, dextromethorphan, metoprolol, paroxetine ). Patients taking medications that are CYP2D6 substrates with quinine sulfate should be monitored closely for adverse reactions a sociated with these medications.

Digoxin: In 4 healthy subjects who received digoxin (0.5 to 0.75 mg/day) during treatment with quinine (750 mg/day), a 33% increase in mean steady state AUC of digoxin and a 35% reduction in the steady-state biliary clearance of digoxin were observed compared to digoxin alone. Thus, if quinine is administered to patients receiving digo xin, plasma digoxin concentrations should be closely monitored, and the digoxin dose adjusted, as necessary.

Halofantrine: Although not studied clinically, quinine was shown to inhibit the metabolism of halofantrine in vitro using human liver microsomes. Therefore, concomitant administration of quinine sulfate is likely to increase plasma halofantrine concentrations.

Mefloquine: In 7 healthy subjects who received mefloquine (750 mg) at 24 hours before an oral 600 mg dose of quinine sulfate, the AUC of mefloquine was increased by 22% compared to mefloquine alone. In this study, the QTc interval was significantly prolonged in the subjects who received mefloquine and quinine sulfate 24 hours apart. The concomitant administration of mefloquine and quinine may produce electrocardiographic abnormalities (including QTc prolongation) and may increase the risk of seizures.

Neuromuscular blocking agents (pancuronium, succinylcholine, tubocurarine): In one report, quinine potentiated neuromuscular blockade in a patient who received pancuronium during an operative procedure, and subsequently (3 hours after receiving pancuronium) received quinine 1800 mg daily. Quinine may also enhance the neuromuscular blocking effects of succinylcholine and tubocurarine .

Warfarin and oral anticoagulants: Cinchona alkaloids, including quinine, may have the potential to depress hepatic enzyme synthesis of vitamin K-dependent coagulation pathway proteins and may enhance the action of warfarin and other oral anticoagulants. Quinine may also interfere with the anticoagulant effect of heparin. Thus, in patients receiving these anticoagulants, the prothrombin time (PT), partial thromboplastin time (PTT), or international normalization ratio (INR) should be closely monitored as appropriate, during concurrent therapy with quinine.

Drug/Laboratory Interactions: Quinine may produce an elevated value for urinary 17-ketogenic steroids when the Zimmerman method is used.