The purpose of this study is to evaluate and compare the relative bioavailability of Quinine
Sulfate 324 mg capsules, manufactured by the Mutual Pharmaceutical Company, to Quinine
Sulphate 300 mg tablets, manufactured by the Government Pharmaceutical Organization, Bangkok
Metropolis, Thailand, after single oral dose administration under fasting conditions. An
additional purpose of this study is to evaluate the effect of food on the Mutual
Pharmaceutical Company product.
one of the three test products (treatment A - quinine sulfate capsules 324 mg, treatment B -
quinine sulphate tablets 300 mg, treatment C - quinine sulfate capsules 324 mg administered
thirty minutes after the initiation of a standardized, high-fat breakfast). Subjects will
fast for 4 hours after dosing. Blood samples will be drawn from all participants before
dosing and for 48 hours post-dose at times sufficient to adequately define the
pharmacokinetics of quinine sulfate under fed and fasting conditions and quinine sulphate
under fasting conditions. Sitting blood pressure and heart rate will be obtained prior to
dosing and at 1, 2, 4 and 12 hours post-dose and upon completion of the study. An
electrocardiogram will be recorded at check-in and at 2, 4, 6, 12, and 24 hours post-dose.
Subjects will be monitored throughout their participation in the study for adverse
reactions.
Minimum age: 18 Years.
Maximum age: N/A.
Gender(s): Both.
Inclusion Criteria:
- Screening Demographics: All volunteers selected for this study will be healthy men or
women at least 18 years of age, inclusive, at the the time of dosing. The weight
range will not exceed ± 20% for height and body frame as per Desirable Weights for
Adults - 1983 Metropolitan Height and Weight Table
- Screening procedures: Each volunteer will complete the screening process within 28
days prior to Period I dosing. Consent documents for both the screening evaluation
and HIV antibody determination will be reviewed, discussed, and signed by each
potential participant before full implementation of screening procedures.
- Screening will include general observations, physical examination, demographics,
medical and medication history, an electrocardiogram, sitting blood pressure and
heart rate, respiratory rate and temperature. The physical examination will include
an evaluation of the cardiovascular, gastrointestinal, respiratory and central
nervous systems.
- The screening clinical laboratory procedures will include:
- HEMATOLOGY: hematocrit, hemoglobin, WBC count with differential, RBC count, platelet
count
- CLINICAL CHEMISTRY: serum creatinine, BUN, glucose, AST(GOT), ALT(GPT), albumin, total
bilirubin, total protein, and alkaline phosphatase
- HIV antibody and hepatitis B surface antigen screens
- URINALYSIS: by dipstick; full microscopic examination if dipstick positive; and
- URINE DRUG SCREEN: ethyl alcohol, amphetamines, barbiturates, benzodiazepines,
cannabinoids, cocaine metabolites, opiates and phencyclidine
- SERUM PREGNANCY SCREEN (female volunteers only)
If female and:
- of childbearing potential, is practicing an acceptable method of birth control for
the duration of the study as judged by the investigator(s), such as condom with
spermicide, diaphragm, intrauterine device (IUD), or abstinence; or
- is postmenopausal for at least 2 years; or
- is surgically sterile (bilateral tubal ligation, bilateral oophorectomy, or
hysterectomy)
Exclusion Criteria:
- Volunteers with a recent history of drug or alcohol addiction or abuse
- Volunteers with the presence of a clinically significant disorder involving the
cardiovascular, respiratory, renal, gastrointestinal, immunologic, hematologic,
endocrine, or neurologic system(s) or psychiatric disease (as determined by the
clinical investigators)
- Volunteers whose clinical laboratory test values are outside the accepted reference
range and when confirmed on re-examination are deemed to be clinically significant
- Volunteers demonstrating a positive hepatitis B surface antigen screen or a reactive
HIV antibody screen
- Volunteers demonstrating a positive drug screen when screened for this study
- Female volunteers demonstrating a positive pregnancy screen
- Female volunteers who are currently breastfeeding
- Volunteers with a history of allergic response(s) to quinine or related drugs
- Volunteers with a history of clinically significant allergies including drug
allergies
- Volunteers with a history of clinically significant illness during the 4 weeks prior
to Period I dosing (as determined by the clinical investigators)
- Volunteers who currently use tobacco products
- Volunteers who have taken any drug known to induce or inhibit hepatic drug metabolism
in the 28 days prior to Period I dosing
- Volunteers who report donating greater than 150mL of blood within 28 days prior to
Period I dosing. All subjects will be advised not to donate blood for four weeks
after completing the study
- Volunteers who have donated plasma (e. g. plasmapheresis) within 14 days prior to
Period I dosing. All subjects will be advised not to donate plasma for four weeks
after completing the study
- Volunteers who report receiving any investigational drug within 28 days prior to
Period I dosing
- Volunteers who report taking any systemic prescription medication in the 14 days
prior to Period I dosing
- Volunteers with QTc >480 msec on the screening electrocardiogram (ECG) or with
clinically significant findings
- Volunteers who have a glucose-6-phosphate dehydrogenese deficiency (G6PD)