Smokers of low-yield, ventilated-filter cigarettes sometimes defeat the purpose of the smoke-dilution holes by occluding them with fingers, lips, or tape. Blocking the holes is shown to have large effects on the delivery by these cigarettes of toxic products (nicotine, tar, and carbon monoxide). Techniques for detecting this misuse of "less hazardous" cigarettes are discussed, with particular emphasis on the distinctive signs of hole-blocking which are left in the spent filters. (Am J Public Health 1980; 70:1202-1203 low-tar smokers have blocked the holes with their fingers, lips or with tape.* Lipstick marks on the holes have proven to be clear-cut indicators of hole-blocking; holding the cigarette between the teeth appears to facilitate the practice of covering the holes with one's lips. A few smokers confess to having held their cigarettes with two hands (the tips of four fingers over the holes) to block the perforations. A simple "'pinch" of the perforations with opposing fingers is a more common method of blocking the holes. The present study reports the extent to which hole-blocking can increase the delivery of tobacco smoke to the smoker. MethodsMost of the apparently least-hazardous of the 'less-hazardous' low-tar, low-nicotine, low carbon monoxide (CO) cigarettes,' achieve their low yields of toxic products by means of ventilation holes in the filters. In 1979, about 25 per cent of all cigarettes sold in the United States had perforated filter tips.2 The rings of perforations cause inhaled tobacco smoke to be diluted with air and thereby decrease the amount of smoke per puff delivered to the smoker.The effects (and frustrations) of ventilated filters can be illustrated by making a ring of small holes about 10 mm from the proximal end of a drinking straw. A desired beverage can still be drunk, but it is adulterated with air and much harder to suck through the straw. Although smoking machines which measure tar and nicotine deliveries do not occlude the perforations, we have found in systematic interviews that 32 per cent to 69 per cent (95 per cent confidence interval) of

The distribution of basic drugs in blood differs qualitatively from that of acidic drugs. The binding of racemic, d-methadone, and l-methadone to human plasma and isolated protein fractions was studied by equilibrium dialysis at 37 degrees. In plasma samples from 29 healthy subjects free fraction of dl-methadone was (mean% +/- SD) 10.62 +/- 1.43. There were significant variations among subjects (p less than 0.001). The free fraction of the d-isomer was 9.24 +/- 1.61% and of the l-isomer, 12.44 +/- 1.53%. Plasma albumin concentration and degree of binding do not correlate, but in normal hypoalbuminemic subjects the free fraction of dl-methadone correlates negatively with the concentration of alpha 1-acid glycoprotein (alpha 1-AGP), an acute-phase reactant protein. Percentage dl-methadone bound to purified human serum albumin (HSA) (4.1 mg/dl) was 36.60% (mean +/- SD). Isolated alpha 1-AGP bound dl-methadone more avidly. As the alpha 1-AGP increased from 0.05 to 2.0 gm/l, free fraction fell from 92.40% to 8.80%. Addition of alpha 1-AGP (0.05 to 2.0 gm/l) to a physiologic concentration of purified HSA or to whole plasma progressively increased methadone binding. In eight monozygotic twin pairs, within-pair differences in binding of dl-methadone were less than in eight dizygotic twin pairs. Less than 20% of naloxone, codeine, morphine, heroin, pentazocine, and diphenoxylate bound to alpha 1-AGP. Elevations of alpha 1-AGP that occur in a variety of diseases may alter the kinetic and pharmacologic activity of methadone.

Phenytoin kinetics during long-term alcohol use and withdrawal were studied in 11 male alcoholics with a history of withdrawal seizures and no evidence of chronic liver disease. Ethanol, 20% v/v, was given for 6 days after admission to maintain the blood alcohol level between 500 and 800 mg/l and phenytoin suspension, 150 mg, was given orally or intravenously (on three occasions) every 12 hr for 20 days. The mean (+/- SD) total phenytoin clearance in 9 of 11 subjects was 0.023 +/- 0.006 l/kg/hr during the alcohol ingestion period. Clearance rose to 0.033 +/- 0.013 l/kg/hr (P less than 0.05) during alcohol withdrawal. Total steady-state concentration after 3 wk ranged from 3.4 to 29.9 mg/l, while the weight-corrected dose range was only 3.7 to 5.5 mg/kg/day. Inter- and intra-subject variation in bioavailability was small (0.93 to 1.03). Phenytoin free fractions ranged from 9.09% to 17.75% and changes in total and free phenytoin concentration correlated (r2 = 0.92, P less than 0.001). The data are compatible with the hypothesis that increased phenytoin clearance during alcohol withdrawal is due to the increased metabolic rate of the drug secondary to enzyme induction by ethanol, which becomes unmasked on cessation of drinking. In most alcoholics standard-dose phenytoin (300 mg/l) will induce lower than usual plasma concentrations.