Figure 1.
Time schedule of meperidine injection.
Full legend: Time schedule of meperidine injection at 9:00 am or 9:00 pm for 5 days and then a 2-day washout period.
Figure 2.
The 24-h rhythm of analgesic effect after meperidine injection.
Full legend: The 24 h rhythm of analgesic effect after meperidine (20 mg/kg i.p.) (▪) or saline (□) injection. Each value represents the mean with SD. *P<0.05, **P<0.01 compared with the saline group using Scheffe's test.
Figure 3.
Influence of dosing time on tolerance after 5-day meperidine injection at day or night.
Full legend: Influence of dosing time on tolerance to analgesia at 30 min after 5-day meperidine or saline injection at 9:00 am or 9:00 pm. Each value represents the mean with SD. *P<0.05, **P<0.01 compared with the corresponding saline group, and #P<0.05, ##P<0.01 comparison between two dosing time using Scheffe's test.
Figure 4.
Influence of dosing time on recovery from tolerance after 2-day washout period.
Full legend: Influence of dosing time on recovery from tolerance after a single meperidine (20 mg/kg i.p.) or saline injection at 3:00 pm, followed by a 2-day washout period after 5-day meperidine or saline injection at 9:00 am or 9:00 pm (□, 9:00 am; ▪, 9:00 pm). Each value represents the mean with SD. *P<0.05, **P<0.01 comparison between groups using Scheffe's test. A, a single saline injection after 5-day saline injection at 9:00 am. B, a single saline injection after 5-day saline injection at 9:00 pm. C, a single meperidine injection after 5-day saline injection at 9:00 am. D, a single meperidine injection after 5-day saline injection at 9:00 pm. E, a single meperidine injection after 5-day meperidine injection at 9:00 am. F, a single meperidine injection after 5-day meperidine injection at 9:00 pm.
Figure 5.
Plasma concentration-time profiles after meperidine injection (20 mg/kg, i.p.) at 9:00 am and 9:00 pm.
(A, C) Plasma concentration-time profiles of meperidine at 9:00 am and 9:00 pm. (B, D) Plasma concentration-time profiles of normeperidine at 9:00 am and 9:00 pm. Each value represents the mean. (n = 7).
Table 1.
Parameters of meperidine and normeperidine after meperidine (20 mg·kg−1, i.p.) injection at 9:00 am or 9:00 pm.