Analgesic dose-response relationship of ibuprofen 50, 100, 200, and 400 mg after surgical removal of third molars: a single-dose, randomized, placebo-controlled, and double-blind study of 304 patients.

The purpose of this single-dose, randomized, placebo-controlled, and double-blind study was to evaluate the analgesic dose-response relationship of 50-mg, 100-mg, 200-mg, and 400-mg doses of ibuprofen after third molar surgery. Patients were instructed to take a single dose of either placebo or 50 mg, 100 mg, 200 mg, or 400 mg of ibuprofen when the postoperative pain was moderate to severe. Acetaminophen 500 mg was used as a rescue medication. Pain intensity, pain relief, and any possible adverse events were recorded on self-administered questionnaires hourly for 6 hours after intake of study medication. If rescue medication was taken, the time of intake was registered. A total of 304 patients entered the study, and 258 complied with the protocol. A positive analgesic dose-response relationship of 50-mg, 100-mg, 200-mg, and 400-mg doses of ibuprofen was observed when evaluated by pain intensity difference, sum of pain intensity difference, pain relief, total pain relief, and survival distribution of patients not taking rescue medication. Although significant pain relief was seen after a dose of 50 mg ibuprofen, ibuprofen 400 mg provided maximum pain relief and the longest duration of analgesic effect. Mild transient adverse events were reported by 6.8% of the patients. However, there was no significant difference in frequency between the placebo and 50 mg, 100 mg, 200 mg, and 400 mg ibuprofen dose groups.

A randomized, double-blind, placebo-controlled, dose-response study of the analgesic effect of lornoxicam after surgical removal of mandibular third molars.

The aim of the present study was to investigate the dose-effect relationship of single doses of 4 to 32 mg of lornoxicam (LNX), a new nonsteroidal antiinflammatory drug belonging to the oxicam group, compared with placebo and 10 mg ketorolac (KET) in the treatment of pain after oral surgery. Also, it was the aim of the study to evaluate the relationship between adverse events and different doses of LNX. After the surgical removal of a mandibular third molar, test medication was taken when the patients experienced at least moderate pain. After medication, pain relief, pain intensity, and any discomfort from the medication were noted in a questionnaire. Paracetamol was used as rescue medication. A total of 278 patients completed the study according to the protocol. The primary efficacy parameter was total pain relief after 6 hours, and all active treatments showed significantly better effect than placebo, with LNX 16 and 32 mg being significantly superior to LNX 4 mg. All other efficacy parameters showed the same dose-effect relationship. A total of 37 adverse events were reported evenly distributed in the 6 treatment groups; only 3 of these were considered severe, and all disappeared without treatment. In conclusion, the study showed a dose-effect relationship of LNX without a rise in adverse events. The effect of 10 mg KET seemed to be at the level of 8 to 16 mg LNX.

Does metronidazole prevent alveolitis sicca dolorosa? A double-blind, placebo-controlled clinical study.

The effect of a single preoperative dose of metronidazole in the prevention of alveolitis sicca dolorosa (ASD) after surgical removal of one impacted, non-infected mandibular third molar was investigated. A patient sample of 270 were given either 1000 mg of metronidazole or placebo at least 30 min before surgery. The preoperative recordings included gender, age, tooth to be removed, experience of surgeon, time of test medication, and duration of surgery. No difference was found between the metronidazole and placebo groups in the occurrence of ASD. The duration of surgery and the experience of the operating surgeons had no effect on the occurrence of ASD. The present study failed to demonstrate any preventive effect of a single dose of metronidazole on the development of ASD.

Codeine in analgesic doses does not depress respiration in patients with severe chronic obstructive lung disease.

Nineteen normocapnic patients with chronic obstructive lung disease participated in an open single dose safety study (part one) followed by a randomized double-blind cross-over study comparing two seven-days treatment periods of 1 g of paracetamol t.i.d. with 60 mg of codeine plus 1 g of paracetamol t.i.d., respectively (part two). In part one, continuous monitoring after a single dose of 2 g of paracetamol and 120 mg of codeine revealed no deterioration in the respiration and gas tensions. In part two, respiratory parameters and arterial gas tensions were recorded one hour after the last morning dose. PaCO2 increased insignificantly (0.05 less than P less than 0.10) by a median of 0.38 kPa during treatment with codeine and paracetamol compared to treatment with paracetamol alone. PaO2 decreased by 0.12 kPa (P greater than 0.10). There was no correlation between changes in PaCO2 and changes in PaO2. FVC, FEV1 and dyspnoea at rest were unchanged. Gastrointestinal side effects were reported significantly (P less than 0.02) more often during treatment with codeine plus paracetamol. There was no correlation between the plasma concentration of codeine or morphine and changes in respiratory parameters or adverse effects. The limitation for the short time clinical use of codeine as an analgesic to normocapnic patients with severe chronic obstructive lung disease in stable phase seem to be gastrointestinal side effects.

The role of vaginal secretory immunoglobulin A, Gardnerella vaginalis, anaerobes, and Chlamydia trachomatis in postabortal pelvic inflammatory disease.

In a prospective study of 129 women undergoing induced first-trimester abortion, 14 (10.9%) contracted postabortal pelvic inflammatory disease (PID). Samples of vaginal secretion for quantitation of secretory immunoglobulin A (sIgA) as well as isolates from cervix/urethra for the culture of anaerobes and aerobes, including Bacteroides fragilis et melaninogenicus and Gardnerella vaginalis, were obtained at the preoperative visit. Two blood samples from each woman with postabortal PID were analysed for antibodies against G. vaginalis. Twenty-five per cent of women with a history of PID developed postabortal PID, and 25% with vaginitis contracted postabortal infection (p less than 0.001 and p less than 0.005). Twenty-five per cent of women harboring C. trachomatis at the time of abortion developed infection. The presence of anaerobes or G. vaginalis was not associated with the frequency of postabortal PID (all p-values greater than 0.1). One woman with postabortal PID produced a culture positive for G. vaginalis and a rise in specific antibody titer. The levels of vaginal sIgA were not significantly associated with a positive history of PID (p greater than 0.6), with postabortal PID (p greater than 0.4) or with the presence of anaerobes or G. vaginalis at the time of abortion (p greater than 0.3). However, significantly elevated levels of sIgA were found in women harboring C. trachomatis (p less than 0.05). Thus, the study could not demonstrate any correlation between vaginal sIgA and PID, but increased sIgA in Chlamydia-positive women. A history of PID and vaginitis entailed a significant risk of contracting postabortal PID.

Blood and milk concentrations of ampicillin in mothers treated with pivampicillin and in their infants.

The levels of ampicillin were determined in milk and plasma of 14 lactating mothers in treatment with pivampicillin for puerperal infections and in plasma of their suckling infants. Ampicillin could not be detected in plasma of the infants, i.e. all levels were less than 0.03 micrograms/ml. Maximum levels occurred in plasma 60-120 minutes and in milk 180-240 minutes after medication. Milk-plasma ratios varied between 0.01 and 0.58. The highest level of ampicillin in milk was 1.02 micrograms/ml in a woman receiving pivampicillin tablets 700 mg t.d.s. At this level an infant can at the most ingest 0.5 mg/day. This dose is too small to cause any symptoms in the suckling infants, but allergic sensibilization through the milk is possible.

Blood and milk concentrations of metronidazole in mothers and infants.

In order to assess the amounts of metronidazole and its clearance in suckling neonates whose mothers received the drug in therapeutic doses, we measured its levels in maternal plasma and milk and in infant plasma. Eleven mothers receiving 600 mg metronidazole daily and 4 receiving 1200 mg and their 15 infants had milk and plasma levels determined with a specific semi-micro high-pressure liquid chromatographic method. Maternal mean plasma levels were 5.0 micrograms/ml, range 1.0 - 11.6 micrograms/ml (600 mg/day) and 12.5 micrograms/ml range 3.7 - 17.9 micrograms/ml (1200 mg/day) and corresponding infant plasma levels were 0.8 micrograms/ml, range 0.3 - 1.4 micrograms/ml and 2.4 micrograms/ml, range 0.6 - 4.9 micrograms/ml. Maternal milk/plasma ratio was 1 and baby/mother plasma ratio was 0.15, independent of dosage (Tab. I). The levels of metronidazole hydroxy metabolite (I) were all below those of metronidazole (Tab. II). Simultaneous milk and blood samples showed almost identical levels (Tab. III). Infant total clearance of metronidazole was calculated to be ca. 60% of maternal clearance by body weight and 24% by body surface, independent of dosage, while maximum infant metronidazole intake was estimated to be 3.0 mg/kg/day assuming a daily intake of 500 ml milk. It is recommended to avoid simultaneous breastfeeding and metronidazole therapy until possible harmful longterm effects on the neonates are known.