Pharmacokinetics of human insulin zinc suspension (recombinant DNA) in normal man: a comparison with porcine insulin zinc suspension.

A single dose crossover study in 10 fasting, non-diabetic men compared the 24-hour profiles of blood glucose, plasma insulin, and C-peptide following a single subcutaneous injection of either human insulin zinc suspension crystalline (recombinant DNA), or highly purified porcine insulin zinc suspension (mixed), in a standard dose of 0.2 U/kg. Both insulins produced moderate hypoglycaemia within 3 hours which persisted for 24 hours after administration. The rate of fall of blood glucose was similar from 0-3 hours but was significantly lower after the porcine insulin at 4 and 7 hours (p less than 0.05). Mean plasma insulin values were higher after porcine insulin between 2 and 6 hours (p less than 0.05) and a biphasic pattern was observed following injection of both insulins. Plasma C-peptide declined after each insulin was administered, and was significantly lower between 2 and 7 hours after porcine insulin. The duration of the hypoglycaemic action of human crystalline insulin (recombinant DNA), assessed by blood glucose measurements and C-peptide suppression, was equivalent to porcine insulin zinc suspension (mixed) (Monotard MC, Novo) over 24 hours.

Pharmacokinetic studies of benoxaprofen in geriatric patients.

Benoxaprofen plasma profiles were obtained in 10 elderly patients (mean age 77 years) suffering from osteoarthritis and various underlying diseases. Blood levels were measured over a 17-day period. Benoxaprofen, 600 mg, was given daily for the first 10 days. The mean peak plasma concentration on Day 1 occurred three hours after the fasting dose. Mean plasma levels on Days 2-10 showed a continuing rise with no indication that a steady-state level was achieved. Elimination half-lives calculated from plasma levels on Days 12-17 resulted in a mean of 101 hours in these elderly patients. This is a substantial increase compared with normal subjects (half-life 30 to 35 hours). Most haematologic and biochemical results were judged to be within the usual range for this type of elderly patient (A.K.) No evidence of renal impairment due to the treatment was shown. The higher benoxaprofen concentrations and the long elimination half-life show evidence of accumulation in the elderly, probably due to several causes, including poor bowel motility and decreased renal clearance common with increasing age. The recommended dose may require modification in geriatric patients.

The pharmacokinetics of benoxaprofen in elderly subjects.

Benoxaprofen plasma profiles were obtained in two groups of elderly female patients. A single dose of benoxaprofen, either 600 mg or 300 mg, was given and blood levels were measured daily to 120 hours. Mean peak plasma levels were reached at five hours following the 600-mg dose and at seven hours after the 300-mg dose. Elimination half-lives calculated from levels during 36-120 hours resulted in means of 111 hours and 86.4 hours for the 600-mg and 300-mg doses respectively. (Normal subjects, 30 to 35 hours.) Because of these extended half-lives, a further study was conducted following a single 600-mg dose to four more patients. Blood vessels were measured up to 504 hours (21 days). This resulted in a means half-life of 147.9 hours calculated from levels during 168-504 hours. Although serum creatinine levels ere not generally above the normal for this age group, calculated creatinine clearances were considerably reduced. It is concluded that the high plasma benoxaprofen levels achieved, combined with the slow clearance rates and long half-lives, indicate that it may be possible to work is needed to determine whether this prolonged half-life is matched by an equally prolonged therapeutic effect.

Multicentre osteoarthritis trial.

A multicentre comparative crossover study of benoxaprofen in the treatment of osteoarthritis was undertaken by general practitioners in the United Kingdom. Rheumatologists from 20 centres helped to coordinate the trial and provided x-ray confirmation of the diagnosis. In predetermined random order, patients were assigned to treatment groups and given either benoxaprofen or one of the comparator drugs (diclofenac, indomethacin, flurbiprofen, or piroxicam) for the first four weeks. Results from the first 1403 completed cases revealed that patients preferred benoxaprofen over all the comparator drugs.

Plasma profiles of two differing doses of fenoprofen in geriatric patients.

Plasma levels after single doses of 300 mg and 600 mg fenoprofen were measured in 10 elderly patients with osteoarthritis. Mean peak concentrations occurred at 4 hours. For the 300 mg dose, this was similar to levels obtained in an earlier study with young volunteers but the drug was absorbed more slowly in the elderly, peak levels being achieved approximately 2 hours later. There was no significant difference in the area under the plasma concentration-time curves compared with previous studies, and plasma levels after multiple doses showed no evidence of drug accumulation. Haematological and biochemical values were within acceptable limits for this patient population. It is concluded that fenoprofen is reliably but more slowly absorbed in the elderly, and that normal dosages can be utilized.