METHAQUALONE-DIPHENEYDRAMINE INTERACTION: A HUMAN STUDY
| dc.creator | Schneider, Colin Brent | |
| dc.date.accessioned | 2024-01-16T17:26:05Z | |
| dc.date.available | 2024-01-16T17:26:05Z | |
| dc.date.issued | 1981 | |
| dc.date.submitted | 1981 | |
| dc.description.abstract | Diphenhydramine inhibits the metabolism of methaqualone, in vitro, by the 10,000 g supernatant fraction of rat liver homogenate (Hindmarsh et al., 1978). When methaqualone is administered orally to rats, with diphenhydramine, blood levels of methaqualone are elevated (two-fold) (Hindmarsh et al., 1979). Further studies have suggested this increase in blood methaqualone levels is due to an inhibition of methaqualone metabolism by the rat intestine (LeGatt et al., 1980). Studies in humans have been inconclusive as to whether a similar interaction occurs in man (Williams et al., 1974a, 1974b). To clarify any interaction between methaqualone and diphenhydramine in humans, a clinical study was conducted with twelve volunteers. Each volunteer received three treatments, methaqualone hydrochloride (250 mg) (Mequelon® ), methaqualone hydrochloride (250 mg) plus diphenhydramine hydrochloride (25 mg) (Mequelon® plus Benadryl® elixir) and Mandrax® (methaqualone (250 mg) plus diphenhydramine hydrochloride (25 mg)), according to a Latin Square design. One subject also received an addi-tional dose, consisting of methaqualone hydrochloride (25() mg) plus diphenhydramine hydrochloride (50 mg) (Mequelon® plus Benadryl® ). Each treatment was separated by a "wash-out" period of at least two weeks. Blood and total urine samples were collected over 48 and 56 hours res-pectively, extracted and subsequently analyzed by GC. Methaqualone and the 2'-hydroxymethyl metabolite were quantitated in blood, the 2'-hydroxyrnethyl, the 2-hydroxymethyl and the 4'-hydroxy metabolite, in urine. Peak blood concentrations of methaqualone ranged from 1.00 pg/mL to 2.66 ug/mL at an average Tax of 1.5 hours. The elimination of methaqualone followed a two-compartment model, with the terminal elimination phase becoming evident approximately twelve hours after administration. Elimination half-lives ranged from 26.8 to 54.1 hours (average of 35.9 hours). The unconjugated 2'-hydroxy-methyl metabolite was the only metabolite detected in blood. Blood metabolite levels increased to a maximum of 157 to 663 ng/mL (average of 314 ng/mL) at 4 - 8 hours after administration of methaqualone and remained at a plateau until the end of the sampling period (48 hours). The average total urinary excretion of the three major metabolites was 2.92 mg for the 2-hydroxymethyl, 6.97 mg for the 2'-hydroxymethyl and 12.18 mg for the 4'-hydroxy metabolite. Total metabolite excretion from 0 to 56 hours was 22.07 mg, or 8.3% of the dose administered. | |
| dc.identifier.uri | https://hdl.handle.net/10388/15436 | |
| dc.subject | methaqualone | |
| dc.subject | diphenhydramine | |
| dc.title | METHAQUALONE-DIPHENEYDRAMINE INTERACTION: A HUMAN STUDY | |
| dc.type.genre | Thesis | |
| thesis.degree.department | Pharmacy | |
| thesis.degree.grantor | University of Saskatchewan | en_US |
| thesis.degree.level | Masters | |
| thesis.degree.name | Master of Science (M.Sc.) |