Figures & data
(A)Mechanism-based pharmacokinetic–pharmacodynamic modeling of the ability of different doses of an opioid antagonist (naloxone, given at t = 55 min, low dose = 0.1 mg, high dose = 0.4 mg) to reverse the opioid-induced respiratory depression from an opioid agonist with relatively low koff value (opioid agonist injected at t = 0 min). The speed of reversal is independent of the antagonist dose and is determined by the agonist opioid receptor koff value. (B) Effect of variations in the koff value of an opioid agonist (injected at t = 0 min over 90 s) on the effect of a fixed dose of an opioid receptor antagonist (naloxone, given at t = 55 min over 90 s) on reversal of opioid-induced respiratory depression.
Koff values are relative with 0.2 min-1 = 0.2 × typical value, 1 = typical value, 5 = 5 × typical value. Here, the typical value = 0.03 min-1.
Koff: Receptor dissociation constant.
Data taken from Citation[17].
![Figure 1. Effect of naloxone on opioid-induced respiratory depression.(A)Mechanism-based pharmacokinetic–pharmacodynamic modeling of the ability of different doses of an opioid antagonist (naloxone, given at t = 55 min, low dose = 0.1 mg, high dose = 0.4 mg) to reverse the opioid-induced respiratory depression from an opioid agonist with relatively low koff value (opioid agonist injected at t = 0 min). The speed of reversal is independent of the antagonist dose and is determined by the agonist opioid receptor koff value. (B) Effect of variations in the koff value of an opioid agonist (injected at t = 0 min over 90 s) on the effect of a fixed dose of an opioid receptor antagonist (naloxone, given at t = 55 min over 90 s) on reversal of opioid-induced respiratory depression.Koff values are relative with 0.2 min-1 = 0.2 × typical value, 1 = typical value, 5 = 5 × typical value. Here, the typical value = 0.03 min-1.Koff: Receptor dissociation constant.Data taken from Citation[17].](/cms/asset/a9f0c456-4804-48dc-a27b-1035c7eba67e/ierj_a_11209454_f0001_b.jpg)
(A) Blockade probabilities after an epidural injection of ropivacaine 125 mg in a 50-year-old patient. The size of the dots is proportional to the probability of blockade with 90% (solid line), 75% (broken line) and 50% (dotted line) isoeffect lines. Time is expressed on the x-axis and the dermatome level on the y-axis. (B) Probability of blockade, P(block), for dermatomes S5 (broken line), Th11 (solid line) and Th7 (dotted line) versus time.
Data taken from Citation[32].
![Figure 2. Population pharmacokinetic–pharmacodynamic modeling of epidural analgesia.(A) Blockade probabilities after an epidural injection of ropivacaine 125 mg in a 50-year-old patient. The size of the dots is proportional to the probability of blockade with 90% (solid line), 75% (broken line) and 50% (dotted line) isoeffect lines. Time is expressed on the x-axis and the dermatome level on the y-axis. (B) Probability of blockade, P(block), for dermatomes S5 (broken line), Th11 (solid line) and Th7 (dotted line) versus time.Data taken from Citation[32].](/cms/asset/22525e85-d413-49c9-b402-79abed75ae42/ierj_a_11209454_f0002_b.jpg)
The analysis objectively divided the total population response into four categories, with (A) no response to treatment, (B) a response in the treatment week only, (C) a long-term response with a slow return towards pretreatment baseline and (D) full recovery.
Data taken from Citation[33].
![Figure 3. Mixture analyses of the effect of a 1-week ketamine treatment (shaded bar) on pain scored in patients with chronic pain.The analysis objectively divided the total population response into four categories, with (A) no response to treatment, (B) a response in the treatment week only, (C) a long-term response with a slow return towards pretreatment baseline and (D) full recovery.Data taken from Citation[33].](/cms/asset/c32284b4-e693-40e7-a324-e6734a190352/ierj_a_11209454_f0003_b.jpg)