Here is more of that article. It is really interesting information- its also great to find information like this. Like I said above this group is not associated with the brand Suboxone. I know this is long but since my link didnt work here it is. Thanks for dissecting some of this! The chart at the bottom didnt copy correctly so FYI (im sure you all can figure it out but just in case) the dosing goes information is in increasing order.
CLINICAL PHARMACOLOGY
Subjective Effects:
Comparisons of buprenorphine with full agonists such as methadone and hydromorphone suggest that sublingual buprenorphine produces typical opioid agonist effects which are limited by a ceiling effect.
In non-dependent subjects, acute sublingual doses of SUBOXONE tablets produced opioid agonist effects, which reached a maximum between doses of 8 mg and 16mg of SUBUTEX. The effects of 16mg SUBOXONE were similar to those produced by 16mg SUBUTEX (buprenorphine alone).
Opioid agonist ceiling effects were also observed in a double-blind, parallel group, dose ranging comparison of single doses of buprenorphine sublingual solution (1, 2, 4, 8, 16, or 32 mg), placebo, and a full agonist control at various doses. The treatments were given in ascending dose order at intervals of at least one week to 16 opioid-experienced, non-dependent subjects. Both drugs produced typical opioid agonist effects. For all the measures for which the drugs produced an effect, buprenorphine produced a dose-related response but, in each case, there was a dose that produced no further effect. In contrast, the highest dose of the full agonist control always produced the greatest effects. Agonist objective rating scores remained elevated for the higher doses of buprenorphine (8-32 mg) longer than for the lower doses and did not return to baseline until 48 hours after drug administrations. The onset of effects appeared more rapidly with buprenorphine than with the full agonist control, with most doses nearing peak effect after 100 minutes for buprenorphine compared to 150 minutes for the full agonist control.
Physiologic Effects:
Buprenorphine in intravenous (2mg, 4mg, 8mg, 12mg and 16 mg) and sublingual (12mg) doses has been administered to non-dependent subjects to examine cardiovascular, respiratory and subjective effects at doses comparable to those used for treatment of opioid dependence. Compared with placebo, there were no statistically significant differences among any of the treatment conditions for blood pressure, heart rate, respiratory rate, O2 saturation or skin temperature across time. Systolic BP was higher in the 8 mg group than placebo (3 hour AUC values). Minimum and maximum effects were similar across all treatments. Subjects remained responsive to low voice and responded to computer prompts. Some subjects showed irritability, but no other changes were observed.
The respiratory effects of sublingual buprenorphine were compared with the effects of methadone in a double-blind, parallel group, dose ranging comparison of single doses of buprenorphine sublingual solution (1, 2, 4, 8, 16, or 32 mg) and oral methadone (15, 30, 45, or 60 mg) in non-dependent, opioid-experienced volunteers. In this study, hypoventilation not requiring medical intervention was reported more frequently after buprenorphine doses of 4 mg and higher than after methadone. Both drugs decreased O2 saturation to the same degree.
Effect of Naloxone:
Physiologic and subjective effects following acute sublingual administration of SUBOXONE and SUBUTEX tablets were similar at equivalent dose levels of buprenorphine. Naloxone, in the SUBOXONE formulation, had no clinically significant effect when administered by the sublingual route, although blood levels of the drug were measurable. SUBOXONE, when administered sublingually even to an opioid-dependent population, was recognized as an opioid agonist, whereas when administered intramuscularly, combinations of buprenorphine with naloxone produced opioid antagonist actions similar to naloxone. In methadone-maintained patients and heroin-dependent subjects, intravenous administration of buprenorphine/naloxone combinations precipitated opioid withdrawal and was perceived as unpleasant and dysphoric. In morphine-stabilized subjects, intravenously administered combinations of buprenorphine with naloxone produced opioid antagonist and withdrawal effects that were ratio-dependent; the most intense withdrawal effects were produced by 2:1 and 4:1 ratios, less intense by an 8:1 ratio. SUBOXONE tablets contain buprenorphine with naloxone at a ratio of 4:1.
Pharmacokinetics:Absorption:
Plasma levels of buprenorphine increased with the sublingual dose of SUBUTEX and SUBOXONE, and plasma levels of naloxone increased with the sublingual dose of SUBOXONE (Table 1). There was a wide inter-patient variability in the sublingual absorption of buprenorphine and naloxone, but within subjects the variability was low. Both Cmax and AUC of buprenorphine increased in a linear fashion with the increase in dose (in the range of 4 to 16 mg), although the increase was not directly dose-proportional.
Naloxone did not affect the pharmacokinetics of buprenorphine and both SUBUTEX and SUBOXONE deliver similar plasma concentrations of buprenorphine. The levels of naloxone were too low to assess dose-proportionality. At the three naloxone doses of 1 mg, 2 mg, and 4 mg, levels above the limit of quantitation (0.05 ng/mL) were not detected beyond 2 hours in seven of eight subjects. In one individual, at the 4mg dose, the last measurable concentration was at 8 hours. Within each subject (for most of the subjects), across the doses there was a trend toward an increase in naloxone concentrations with increase in dose. Mean peak naloxone levels ranged from 0.11 to 0.28ng/mL in the dsose range of 1-4 mg.
Table 1. Pharmacokinetic parameters of buprenorphine after the administration of 4 mg, 8mg, and 16 mg Suboxone® doses and 16mg Subutex® dose (mean (%CV)).
Pharmacokinetic Parameter Suboxone®
4 mg Suboxone®
8 mg Suboxone®
16 mg Subutex®
16 mg
Cmax, ng/mL 1.84(39) 3.0(51) 5.95(38 ) 5.47(23)
AUC0-48,
hour. ng/mL 12.52(35) 20.22 (43) 34.89 (33) 32.63 (25)