General information is requested about how to dose drugs and especially antibiotics to pregnant wom

Fråga: General information is requested about how to dose drugs and especially antibiotics to pregnant women. There has been a statement that one should double the dose. Is this correct?

Sammanfattning: "Little information is available on changes of antibiotic doses in pregnant women except for ampicillin which is suggested to be doubled to reach the ""normal"" concentration in pregnant women. This could be not necessary for the urinary infections. More studies with adequate controls are needed for other antibiotics on pharmacokinetic changes during pregnancy. In some serious infections, however, doses should preferentially be modified according to the drug monitoring. As metabolic clearance is increased for some drugs e.g. metoprolol, theophylline and antiepileptics one should consider more frequent plasma concentration monitoring than usual."

Svar: Only few studies have been published in which it is suggested that serum levels of antibiotics in pregnant women differ from those found in other patients. The overall impression from the available data is that the serum levels of many antibiotics may be lower during pregnancy (1).

Alterations in pharmacokinetics of ampicillin in pregnancy have been demonstrated in a crossover study in 26 women, 9-36 weeks pregnant, with lower urinary tract infections (2). Ampicillin was administered intravenously as well as orally. Each woman served as her own non-pregnant control receving identical doses after pregnancy. Plasma levels were found to be 50 per cent lower in pregnant woman than in the same woman when not pregnant. By doubling the dose to 1.0 gram of ampicillin given to pregnant women their plasma levels were increased to those reported earlier by the same author in nonpregnant women following a dose of 0.5 gram (3).

The other antibiotics which seem to show lower plasma levels in pregnant women than those in non-pregnant women include: methicillin, pivampicillin, cephalexin, cephalothin, cephazolin, cephacetrite, erythromycin, gentamicin, kanamycin, amikain, nitrofurantoin and so on. However, most of the above studies are carried out without adequate controls, the lower antibiotic levels in serum or plasma therefore, can only be anticipated.

Pregnancy is associated with alterations in many physiological functions (4,5). The total body water increases by as much as 8 liters during pregnancy, which provides a substantially increased volume within which drugs can be distributed. Gastro-intestinal motility decreases and hence the gut transit time is prolonged. Liver metabolism increases and makes such drugs showing large increases in clearance during pregnancy as phenytoin and metoprolol (6). Glomerular filtration rate rises in pregnancy by 40 to 50 per cent of the non-pregnant mean which is probably a simple reflection of the renal blood flow and does not change independently (8). The renal clearance of theophylline can be increased during pregnancy (9). In a recent review of general principles for prescribing in pregnancy (4) this information is forwarded and a general advice to do more frequent monitoring of plasma concentrations is given. However this author gives no specific advice about how to change doses in pregnant women other than doubling the dose of ampicillin when used to treat a systemic infection. In urinary infections no change is considered necessary.

The major consequence of these physiological changes is the reduction of blood concentration of certain drugs. Fortunately, in most therapeutic circumstances, the doses of antibiotics used produce serum levels well in excess of those required for effective control of the infection. Therefore, the altered kinetics may not be criticial. There are, however, circumstances in which this might be crucial, such as serious infections or infections involving highly resistant bacteria. In such situation, doses might well be modified, based on measured serum concentrations (7). 1 Philipson A: Pharmacokinetics of antibiotics in pregnancy and labour. Clin Pharmacokinet 1979; 4: 297-309 2 Philipson A: Pharmacokinetics of ampicillin during pregnancy. J Infect Dis 1977; 136: 370-376 3 Philipson A: Plasma levels of ampicillin in pregnant women following administration of ampicillin and pivampicillin. Am J Obstet Gynecol 1978; 130: 674-683 4 Rubin PC: Prescribing in pregnancy. General principles. Br Med J 1986; 293: 1415-1417 5 Krauer B, Krauer F: Drug kinetics in pregnancy. Clin Pharmacokinet 1977; 2: 167-181 6 Högstedt S: Hypertension in pregnancy. An epidemiological, clinical and experimental study with special reference to metoprolol treatment. Diss. Uppsala, Uppsala University 1986. 7 Schwarz RH: Considerations of antibiotic therapy during pregnancy. Obstet Gynecol 1981; 58(suppl): 95S-99S 8 Davison JM, Hytten FE: Glomerular filtration during and after pregnancy. J Obstet Gynecol Br Commonwealth 1974; 81: 588-595 9 Frederiksen MC, Ruo TI, Chow MJ, Atkinson AJ Jr: Theophylline pharmacokinetics in pregnancy. Clin Pharmacol Ther 1986; 40: 321-328