Peak blood alcohol prediction: an empirical test of two computer models

OBJECTIVE: Two computer programs (Computerized Blood Alcohol Calculator and Blood Alcohol Content Estimator) were compared for reliability in predicting peak blood alcohol concentration (BAC). METHOD: Subjects were middle-aged volunteers (N = 40; 20 men, 20 women) who each consumed a constant amount of alcohol (40 ml of 95% alcohol or 30 g ethanol) prior to undergoing breath testing to determine peak BAC. The observed BACs were compared with the predicted BACs obtained with each of the computer programs. RESULTS: The Computerized Blood Alcohol Calculator provided marginally better BAC predictions than did the Blood Alcohol Content Estimator. However, both computer models seriously underestimated the peak BACs for this group of subjects. CONCLUSIONS: Results are discussed with particular reference to the need for additional studies of age, gender, and body composition in predicting peak BACs for heterogeneous subject groups.     

Gender comparison of alcohol exposure on drinking occasions

OBJECTIVE: This study was designed to assess the influence of gender, age, drinking style and other selected demographic variables on the rate of alcohol beverage consumption on drinking days. The data were used to predict possible differences in ethanol exposure levels (peak blood alcohol concentration [BAC]) among the subgroups examined. METHOD: A representative sample (N = 2,627) of the U.S. adult population was surveyed using computer-assisted telephone interviewing to assess alcohol use (past 12 months) in quantity, frequency and type of beverage, as well as the time (minutes) usually required to consume the typical quantity of alcohol on drinking days. RESULTS: Of the 1,833 current drinkers (1,028 men, 805 women), women reported consuming a mean of 2.2 standard drinks (1 drink = 12 g ethanol) on typical drinking occasions (days); men reported consuming a mean of 3.2. The duration of the drinking episode was similar for women (122 minutes) and men (126 minutes). The hourly rate of drink consumption was thus lower for women (approximately 1.1 drinks/hour) than for men (approximately 1.6 drinks/hour). For both men and women, there was an age-related increase in the frequency of drinking but a decrease with age in predicted peak BACs and in the alcohol intake per drinking episode. Peak BACs achieved during typical drinking episodes were estimated to be quite similar for men (0.037) and for women (0.036) when prediction equations were based on equal rates of alcohol elimination in both genders. The estimated peak BACs were lower in women than in men when the prediction equation assumed a higher rate of ethanol elimination in women. CONCLUSIONS: Information on the rate of alcohol beverage consumption on drinking days facilitates prediction of BACs typically experienced in men and women of different demographic group memberships. The exposure values obtained will depend upon as yet unsettled norms for ethanol elimination rates in men and women.     

The influences of age and gender on blood ethanol concentrations in healthy humans

OBJECTIVE: Previous cross-section studies suggested that blood ethanol concentrations (BAC) increase with age. To establish this, and to account for putative gender differences, we studied four cohorts of nonalcoholic subjects. METHOD: Fifty-seven subjects were studied: 14 men and 14 women in the young (21-40 years) and 14 men and 15 women in the old (> or = 60 years) groups. All subjects received ethanol (0.3 g/kg) on three occasions: orally (PO) after an overnight fast; PO after a standard meal; and by intravenous (IV) infusion after a standard meal. RESULTS: In all four cohorts, PO ethanol in the fasted state produced the greatest average areas under the curve (AUC) for ethanol, followed by IV ethanol and PO ethanol, both in the fed state. Pooled by age, blood ethanol AUCs were significantly greater in old subjects given PO ethanol when fasted (p = .001) and IV ethanol when fed (p < .004) but not after PO ethanol in the fed state. Pooled by gender, blood ethanol AUCs did not separate men and women in any of the experiments. Corrected for relative volumes of distribution (Vdist) among the four cohorts, only elderly women evidenced AUC values that could not be explained by Vdist alone and only in the fasted state. Both elderly men and women in the fasted state showed higher average peak ethanol levels than gender-matched younger cohorts; this effect was most pronounced in elderly women (47% vs 12%). CONCLUSIONS: The data confirm the influence of age, but fail to confirm that of gender, on blood ethanol response after a moderate dose of ethanol. They also show that feeding state can negate differences due to Vdist alone. In the fasted state, Vdist alone explains AUC and peak increases in elderly men but not in elderly women. Neither gastric metabolism nor motility account for age/BAC differences since these were independent of route. These data suggest caution for elderly drinkers or for those prescribing alcoholic beverages to elderly persons as well as for studies of ethanol ingestion that do not account for age and for feeding state.     

Arterial-venous blood alcohol concentration gradients

Arterial and venous blood alcohol concentration (BAC)-time courses were completely defined in the peripheral circulations, both during and after the constant rate infusions of ethanol via the cephalic vein or hepatic artery in the dog. These BAC data were characterized by the following trends. (1) A much faster rise in the blood alcohol curve, as well as a higher peak BAC was found using the shorter infusion time. (2) During infusion, the alcohol concentration was higher in arterial or arterialized blood than venous blood when infusion was via the cephalic vein. (3) Peak BAC was higher in the femoral artery than the femoral vein whether infusion was via the cephalic vein or hepatic artery. (4) Peak BAC was higher in the hepatic artery or portal vein than the hepatic vein when infusion was via the cephalic vein. When administration was directly into the liver, the peak BAC in the hepatic vein was higher than the portal vein. (5) After infusion ceased, there was an arterial-venous inversion; peripheral arterial ethanol concentrations were significantly less (p<0.001)than corresponding venous concentrations; with cephalic vein administration, a hepatic vein-portal crossover was observed, the reverse being true when ethanol was administered via the hepatic artery. In either case, the BAC was observed to be higher in the hepatic artery than the portal vein or hepatic vein throughout the sampling period. (6) BAC was observed to be higher for the same sampling times at the respective sites when ethanol was administered directly into the liver. While the methodology in this study is prohibitive for human experimentation, correlations may be extended to man. The elaboration of the arterial-venous concentration differences for ethanol should prove beneficial in revealing the relationships among the doses of alcohol, the circulating blood ethanol concentrations, and physiological and psychomotor test parameters in man.This work was supported in part by a grant from The University of Connecticut Research Foundation.Abstracted in part from a dissertation by J. L. Rheingold submitted to The University of Connecticut in partial fulfillment of the Doctor of Philosophy degree requirements.     

Acute alcohol intoxication, body composition, and pharmacokinetics.

The present study compared alcohol pharmacokinetics associated with body weight, anthropometrically estimated total body water, and body mass index in men and women in two experimental sessions, single dose and double dose. All subjects were given the same amount of alcohol (2.3 and 4.6 oz. 86 proof vodka for single dose and double dose, respectively). Data analyses found a significant correlation between body mass index and peak blood alcohol concentration (BAC). Weight and total body water were not significantly correlated with peak BAC. The findings suggested that body mass index may be considered a better criterion than body weight for equating alcohol doses.     

Faster absorption of ethanol and higher peak concentration in women after gastric bypass surgery

AIMS: To investigate the absorption, distribution and elimination of ethanol in women with abnormal gut as a result of gastric bypass surgery. Patients who undergo gastric bypass for morbid obesity complain of increased sensitivity to the effects of alcohol after the operation. METHODS: Twelve healthy women operated for morbid obesity at least 3 years earlier were recruited. Twelve other women closely matched in terms of age and body mass index (BMI) served as the control group. After an overnight fast each subject drank 95% v/v ethanol (0.30 g kg-1 body weight) as a bolus dose. The ethanol was diluted with orange juice to 20% v/v and finished in 5 min. Specimens of venous blood were taken from an indwelling catheter before drinking started and every 10 min for up to 3.5 h post-dosing. The blood alcohol concentration (BAC) was determined by headspace gas chromatography. RESULTS : The maximum blood-ethanol concentration (Cmax) was 0.741 +/- 0.211 g l-1 (+/- s.d.) in the operated group compared with 0.577 +/- 0.112 g l-1 in the controls (mean difference 0.164 g l-1, 95% confidence interval (CI) 0.021, 0.307). The median time to peak (tmax) was 10 min in the bypass patients compared with 30 min in controls (median difference -15 min (95% CI -10, -20 min). At 10 and 20 min post-dosing the BAC was higher in the bypass patients (P < 0.05) but not at 30 min and all later times (P > 0.05). Other pharmacokinetic parameters of ethanol were not significantly different between the two groups of women (P > 0.05). CONCLUSIONS: The higher sensitivity to ethanol after gastric bypass surgery probably reflects the more rapid absorption of ethanol leading to higher Cmax and earlier tmax. The marked reduction in body weight after the operation might also be a factor to consider if the same absolute quantity of ethanol is consumed.     

Acute recovery and tolerance to low doses of alcohol: Differences in cognitive and motor skill performance

Two groups of male social drinkers were trained on a coding and pursuit rotor (PR) task, and then were tested on these two tasks under either alcohol (0.88 ml 94.6% alcohol/kg) or placebo. These treatments were repeated four times at weekly intervals, with similar blood alcohol concentrations (BAC, P>0.50) attained on all sessions (mean peak=0.082%). Drug-free coding and PR, tested prior to each drinking session, revealed no group differences or change during the course of the experiment. On initial drinking sessions, coding was disrupted (P<0.02) at rising BAC levels where PR failed to reveal impairment (P>0.50). However, immediately after peak BAC was reached, acute recovery was evident in coding at a falling BAC were PR remained impaired (P<0.01). These differences in impairment between tasks on the two limbs of the BAC curve suggested that conflicting evidence on the sensitivity of various tasks to alcohol effects may be obtained when studies examine task performance without respect to the limb of the BAC curve. Coding and PR also were differently affected by repeated exposure to alcohol. At later drinking sessions, tolerance was evident in coding, but the impairment in PR remained (P<0.01). Since the task that recovered more swiftly from a single dose of alcohol also revealed faster development of tolerance, it was suggested that the phenomena of acute recovery and tolerance may be positively correlated, and different for different types of tasks.     

The development of alcohol tolerance: acute recovery as a predictor

Two experiments examined individual differences in the rate of alcohol tolerance development as a function of acute recovery. Male social drinkers (n=18) were trained on a complex psychomotor task and subsequently returned for four drinking sessions in which they received the same dose (0.84 ml absolute alcohol/kg) and performed the task at intervals while blood alcohol concentrations (BAC) rose and fell (peak BAC=77.2 mg/dl). A subject's acute recovery from the impairing effect of alcohol during session 1 was measured by the difference in his performance at the same BAC on the rising and the falling limb of the curve. Rate-of-tolerance development was measured by the rate of change in the subject's average impairment under the alcohol during sessions 1–4. Acute recovery scores in both experiments significantly predicted the rate at which tolerance developed, accounting for 64% of the variance in these scores (P<0.0001). Subjects who displayed more acute recovery developed tolerance more quickly. The evidence was considered to imply that the same process may give rise to both acute recovery and tolerance.     

Acute alcohol intoxication in socially drinking female and male offspring of alcoholic fathers

Alcohol pharmacokinetics, mood-state alterations and psychomotor performance were investigated in women and men at risk for developing alcoholism. Estimated body water was used to calculate the alcohol dose in an effort to eliminate differences in alcohol pharmacokinetics between women and men due to differences in body composition. Differences were not detected between women and men or family history groups (family history positive, FH +, and family history negative, FH-) on absorption time, peak blood alcohol level (BAL), elimination time, or area under the blood alcohol curve (AUC). FH + men reported no central stimulant effects at peak BAL on the Sensation Scale, whereas FH- men and women all reported central stimulant effects. Further, FH + men reported a decrease in anxiety after the ingestion of alcohol. Acute intoxication did not affect performance in the FH + group on a finger-tapping task. In the FH - group, the dominant hand was significantly impaired during the ascending limb of the blood alcohol curve and recovered during the descending limb. Differences between family history groups or sex were not detected on a grooved-pegboard task. Results indicated that FH + men may experience alcohol differently from the FH - group and FH + women. FH + women also showed different reactions to acute alcohol than the FH - group. However, these differences were not as consistent across tasks.     

The pharmacodynamics of ethanol: effects on performance and judgment

The objective and subjective effects produced by increasing and decreasing ethanol concentrations were studied in healthy volunteers on three separate occasions. A randomized, double-blind, placebo-controlled, four-way crossover study was used to determine whether there is any disparity between the time course of blood ethanol concentration and its effects on either objective test performance or self rated impairment. On each study day the subjects received one of four treatments consisting of either placebo or sufficient alcohol to achieve peak estimated blood alcohol concentration (Est.BAC) of 0.07 gm/dL, 0.1 gm/dL or 0.14 gm/dL. Est.BAC determined from breath alcohol concentrations were measured 20 minutes after each "dose" until peak Est.BAC was achieved, then 1, 2, 3.5, and 4.5 hours after peak Est.BAC. Digit symbol substitution (DSS), simulated driving reaction time (SDRT), choice reaction time (CRT) and self assessment of impairment (SRI) were measured simultaneously with Est.BAC. Changes in objective performance test scores were well correlated with Est.BAC (r2 = 0.60 P less than .01). Maximum impairment in test performance occurred at the same time as peak Est.BAC. Threshold Est.BAC needed to produce changes in objective test scores greater than placebo were 0.06 +/- 0.01 for DSS, 0.04 +/- 0.01 for SDRT, and 0.04 +/- 0.02 for CRT. There was no evidence of between dose or within dose tolerance to the effects produced by various Est.BAC on any of these performance tests. Subjects' self rated degrees of impairment at various Est.BAC were influenced by whether alcohol concentrations were rising or falling. Subjective impairment ratings were greater while alcohol concentrations were increasing compared to the same Est.BAC occurring during falling alcohol concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)     

One-month repeatability of alcohol metabolism, sensitivity and acute tolerance

Subjects (N = 34) in the Colorado Alcohol Research on Twins and Adoptees (CARTA) were brought back between 30 and 60 days after their initial testing to be retested on all the CARTA procedures. As before, subjects were given a dose of alcohol (.8 g/kg of body weight) calculated to bring their blood alcohol level (BAL) to near 100 mg/dl. Additional doses were given at the end of each of the next 2 hours to maintain their BAL near peak for approximately 3 hours. Repeatability (test-retest correlation) for alcohol clearance rate was near 0, with repeatabilities between .40 and .55 for peak BAL, time-to-peak BAL, average session BAL and relative volume of alcohol distribution. Repeatabilities of prealcohol baseline scores were generally high (median, .71) for the CARTA battery of physiological, motor coordination, perceptual speed and reaction time measures, but were only low to moderate for sensitivity scores (median, .27) and acute tolerance scores (median, .25) calculated on these measures. There was some evidence that repeatabilities for alcohol metabolism, sensitivity and acute tolerance were lower for women than for men.     

Auditory threshold reduction on alcohol ingestion

RATIONALE: Auditory threshold (AT) measurement method has become the standard behavioral procedure for describing auditory sensitivity. Therefore, the AT measurement method is applicable to evaluation of auditory function. However, only a few studies have been performed to clarify the alteration of audibility under the influence of alcohol on normal humans by measurement of AT. OBJECTIVE: The fact that blood alcohol concentration (BAC) is influenced by the dose of alcohol and the time of measurement suggests that the effects of alcohol may also be altered by the same factors. The present study was conducted to elucidate how alcohol ingestion method affects the AT at a wider range from lower to higher frequency in the time course. METHODS: Fifteen paid Japanese (seven men and eight women, 20-33 years of age) were employed in AT measurements at an octave frequency ranging from 250 to 8,000 Hz before and 5, 30, 60, 120, 240 and 480 min after drinking various amounts (125, 250, 500 and 1,500 ml) of normal beer (5% alcohol) or alcohol-free beer. Results: The AT was significantly reduced within 30 min after the ingestion of 250 and 500 ml of beer, occurring on and after peak BAC. The reducing effect disappeared 480 min after ingestion. CONCLUSIONS: Drinking extra small amounts of alcohol induces the reduction of AT. The effect of alcohol on AT is altered by the alcoholic dose used in testing.     

Extroversion, anxiety and the perceived effects of alcohol

To test the hypothesis that personality characteristics are related to alcohol-effect expectancies, 256 (115 men) college students were divided into groups on the basis of self-reported alcohol consumption and anxiety and introversion scores on the Sixteen Personality Factor Questionnaire. Three-way multivariate analyses of variance were conducted to determine expectancy differences by drinking behavior, personality characteristics and sex. Alcohol expectancy scores were found to vary with drinking behavior and personality measures. Elevated expectancy scores were associated with higher quantity-frequency measures of drinking; however, no significant sex differences were obtained. Extroverted students expected more social and physical pleasure, more relaxation and less arousal with drinking. Students with higher levels of trait anxiety expected more global positive changes, sexual enhancement, social assertion and arousal. The association of drinking behavior and personality with expectancies appears to be independent and additive.     

Effect of opioid substitution therapy on alcohol metabolism

Forty opioid substitution patients (methadone, n = 14; LAAM, n = 14; and buprenorphine, n = 12) who were participating in a study on the impact of opiate substitution treatment on driving ability and 22 non-opiate-using control subjects were administered 14.7 g/70 kg of alcohol in two separate sessions, one 2-3 hours before opioid pharmacotherapy dosing and the other 1-2 hours after dosing. The mean blood alcohol concentration (BAC) in the post-opioid dose session was significantly lower than that in the pre-opioid dose session (p < .05). There was a significant effect of experimental group (LAAM, methadone, buprenorphine, or control) on BAC in sessions conducted 1-2 hours after the opioid substitution dose (p < .01). There was a trend for a reduced effect of experimental group on BAC in the pre-opioid substitution dose session (p = .06). The BAC of non-opioid substitution control subjects was significantly higher than that of the LAAM (before and after LAAM dosing) and methadone (after methadone dosing; p < .05) patients. These findings provide evidence for the first time of an interaction between opiates and alcohol in humans that is strongest at the time of peak opiate plasma levels in the hours after opioid dosing.     

Development of dosing guidelines for reaching selected target breath alcohol concentrations.

OBJECTIVE: This study evaluated gender-specific ethanol dosing protocols that were designed to result in one of two peak breath alcohol concentrations (BrACs)--0.07 or 0.10 g/2101. Inter- and intrasubject variability in BrAC were assessed and several possible methods for reducing variability in BrAC were evaluated. METHOD: Subjects (16 women, 16 men, ages 21-30 years) were studied after low (women 0.49 g/kg, men 0.53 g/kg consumed over 10 minutes) and high (women 0.81 g/kg, men 0.89 g/kg consumed over 20 minutes) ethanol doses, consumed following a 4-hour fast. All subjects were regular drinkers. RESULTS: Mean (+/-SD) peak BrACs actually achieved were 0.069+/-0.011 g/2101 after the low dose, and 0.105+/-0.014 g/2101 after the high dose. Mean values for peak BrAC, time to peak BrAC and area under the curve were not statistically significantly different between genders at either dose. BrACs varied by as much as twofold between subjects after equivalent gender and body weight adjusted doses. There was some reproducibility of ethanol pharmacokinetic parameters over dose and time in men, but not in women. CONCLUSIONS: The doses used resulted in equivalent mean ethanol exposures for women and men at each dose, with mean peak BrACs that closely approached the targets, but there was substantial inter- and intrasubject variability in ethanol pharmacokinetics.     

SmartStart: Results of a large point of entry study into preloading alcohol and associated behaviours

BackgroundThere is a growing trend of preloading with alcohol before entering entertainment districts. It is claimed that this occurs to save money and that preloading may be a good indicator of harmful drinking and risk taking behaviours more generally. No study has collected data from a large sample as the participants entered entertainment districts and measured blood alcohol concentration (BAC) levels and self-reported drinking and risk taking behaviours in a systematic way.MethodsIn this research, police and academics worked together to gauge the breadth and depth of preloading behaviours. In all, 3039 people completed a questionnaire and were breathalysed as they entered entertainment districts in Queensland, Australia. Of those, 2751 represented people from Brisbane and this data, collected every Thursday night to Sunday morning during the warm months, was analysed.ResultsMore than 79% of people reported to preload and 71% returned a BAC greater than zero, both with little difference between the genders. Of preloaders, the mean BAC was 0.071, with ‘to socialise with friends’ being the primary reason given for preloading. Increasing preloading BAC was related to increasing risk taking and antisocial behaviours, as well as alcohol abuse and dependence. Older people entering entertainment districts had more accurate estimates of their BAC, yet 20% of our sample did not understand how the BAC system worked. Conducting the research was associated with a higher access rate to police and a lower arrest rate in the areas of data collection in comparison to the same nights 1 year earlier.ConclusionPreloading is widespread and involves moderate to heavy drinking in the Australian population visiting entertainment districts. Any interventions to curb drinking behaviours and reduce violence in night time entertainment districts need to involve approaches aimed at cultural phenomena, such as preloading behaviours.     

Cigarette smoking by women: interactions with alcohol use

Cigarette smoking increased during alcohol self-administration in comparison to an alcohol-free baseline in 24 women given access to alcohol for 21 days. Heavy smokers (25 or more cigarettes per day) increased smoking significantly during drinking (P<0.05). Analysis of tobacco smoking by level of alcohol consumption showed that both heavy and moderate alcohol users increased smoking significantly during alcohol availability (P<0.05, 0.01). The heavy and moderate smokers smoked significantly more between noon and midnight (P<0.001) than at other times when alcohol was available. The rate of cigarette smoking (defined by inter-cigarette intervals) was faster during alcohol self-administration than during the alcohol-free baseline. Heavy smokers smoked most cigarettes at intervals of 11–20 min during heavy or moderate drinking. During the pre-alcohol baseline, these women smoked most cigarettes at intervals of 21–30 or 31–40 min. Most women (70–74%) also increased tobacco smoking at the premenstruum. Both heavy and occasional smokers increased smoking at the premenstruum significantly more than the moderate smokers (P<0.05). All women reported increased psychological discomfort at the premenstruum on the Premenstrual Assessment Form (PAF) but reports of physical discomfort were more marked in women who smoked less at the premenstruum. These data extend previous findings in men that alcohol consumption is associated with increased cigarette smoking to female social drinkers.     

Do breath tests really underestimate blood alcohol concentration?

It has been reported that in the fully postabsorptive state, breath test results underestimate actual blood alcohol concentration (BAC) in 86% of the population. Reanalysis of the data on which this conclusion was based indicates 77% of these subjects were actually underestimated, and 23% were overestimated. Further refinements indicate 68% had their actual BAC underestimated, 16% were acceptably close to the actual BAC, and 16% were overestimated. Perhaps more importantly, comparison of this data with other results indicates fully postabsorptive status may not occur until more than three hours after drinking. Consequently, breath test results may tend to overestimate actual BAC for significant amounts of time after the peak BAC has been reached.     

Neurocognitive impairment due to chronic alcohol consumption in an American Indian community

OBJECTIVE: Studies have shown that clinically ascertained alcoholics tend to have lower scores than nonalcoholics on cognitive performance tests, particularly the Block Design (BD) and Digit Symbol (DS) tests of the Weschler Adult Intelligence Scale-Revised (WAIS-R). The aim of this study was to determine whether similar differences are found in a community sample of Plains Indian men and women with an episodic pattern of drinking and a high lifetime prevalence of alcoholism (71% for men, 44% for women). METHOD: We administered a truncated form of the WAIS-R to 334 members of a Plains Indian tribe (197 women and 137 men). Blind-rated psychiatric diagnoses were assigned according to Diagnostic and Statistical Manual of Mental Disorders, Third Edition (DSM-III-R) criteria and based on the Schedule for Affective Disorders, Lifetime Version (SADS-L) interview. We compared 68 currently drinking alcoholics (38 men and 30 women), 116 abstaining alcoholics (59 men and 57 women) and 150 nonalcoholics (40 men and 110 women). RESULTS: Current and past heavy drinking had no impact on WAIS-R scores in women. Male alcoholics who were abstinent > or = 2years had similar scores to nonalcoholic men. Male current drinkers showed a trend for lower overall verbal and performance (PIQ) scores and BD performance subtest. Further analysis showed that drinking for > or = 15 years was significantly associated with reduced DS in male current drinkers. CONCLUSIONS: These findings suggest that for the men in this community sample, the impact on PIQ is due to the direct effect of chronic alcohol consumption on cognitive performance and is at least partially reversible after 2 years of abstinence.     

Domperidone and levodopa in Parkinson''s disease

To study the absorption of levodopa and interaction with the extracerebral dopamine antagonist domperidone, 15 patients with idiopathic Parkinson's disease were given levodopa 500 mg p.o., alone, and with domperidone pre-treatment. Domperidone pretreatment (10, 20, 40 mg, p.o., i.v. or i.m.) caused a mean 12% increase in peak plasma levodopa concentration, which occurred a mean of 10 min earlier than when levodopa was given alone. Parkinsonian disability scores were improved and peak clinical response occurred 16 min earlier with domperidone than without. Domperidone slightly increases the immediate bioavailability (over 4 h) and anti-parkinsonian response to a given dose of levodopa.