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Biomedical subjects

H C Atkinson

Publications and source records attributed to H C Atkinson.

26 records · Page 2Linked to original sources
PubMed1989

Individualised aminoglycoside dosage based on pharmacokinetic analysis is superior to dosage based on physician intuition at achieving target plasma drug concentrations.

1. A prospective randomised trial was conducted to compare aminoglycoside dose prediction based on individually measured pharmacokinetic data, with dosage based on physician intuition. 2. After 2 days of therapy more patients in the pharmacokinetic group had achieved both peak (6-10 mg 1(-1] and trough (1-2 mg 1(-1] target plasma concentrations (P = 0.007), peaks alone (P = 0.01) and troughs alone (P = 0.01). Their mean (s.e. mean) peak concentration was 6.49 +/- 0.39 mg 1(-1) compared with 4.27 +/- 0.52 mg 1(-1) in the control group (P = 0.001), with trough concentrations of 1.44 +/- 0.22 mg 1(-1) and 0.94 +/- 0.21 mg 1(-1) respectively (P = 0.054). 3. After 5 days of therapy, peak and trough concentrations were still significantly higher in the pharmacokinetic group despite empirical dose adjustment (P = 0.01 and P = 0.013 respectively). 4. The mean (s.e. mean) daily dose of aminoglycoside was higher in the computer group (312 +/- 17 mg vs 203 +/- 13 mg, P = 0.001). 5. These findings suggest that dose estimation based on measured pharmacokinetic parameters is superior at achieving target plasma drug concentrations.

Adult↗
PubMed1988

Relationship between human milk lipid-ultrafiltrate and octanol-water partition coefficients.

The distribution into human milk lipid of 16 drugs with widely varying lipophilicity is reported. There is a high degree of correlation between milk lipid-ultrafiltrate and octanol-water partition coefficients, measured at 37 degrees C, provided digoxin and prednisolone are excluded. These steroid-based molecules may interact with free fatty acids in milk, forming micelles and thus perturbing the milk lipid-ultrafiltrate relationship. Equations are described which enable estimation of drug distribution into milk for lipid-soluble drugs, based on drug pKa and octanol-water partition coefficients.

Female↗
PubMed1988

Prediction of drug concentrations in human skim milk from plasma protein binding and acid-base characteristics.

1. Protein binding in human skim milk of a series of seven drugs with diverse plasma protein binding and acid-base characteristics, was measured by ultrafiltration. 2. A mathematical relationship between plasma and skim milk unbound fractions was established using measured values from this study along with values from the literature. 3. The relationship enables prediction of unknown protein binding values of drugs in skim milk from known plasma protein binding values. 4. Knowledge of milk protein binding enables a more accurate assessment of total milk concentrations than is available from existing theory which is limited to prediction of unbound drug.

Acid-Base Equilibrium↗
PubMed1988

The binding of drugs to major human milk whey proteins.

The binding of nine drugs of diverse physicochemical characteristics to major human milk whey proteins is reported. This group included acids, bases and neutral drugs. No drug bound to alpha-lactalbumin, which is the protein present in greatest concentrations in mature milk. Four drugs, diclofenac, phenytoin, prednisolone and warfarin, bound to albumin but to a much lesser extent than in plasma, consistent with quantitatively less albumin in milk. None of the basic drugs studied bound to albumin. Five drugs, atenolol, diclofenac, prednisolone, propranolol and warfarin, bound to lactoferrin though the extent was minimal except for diclofenac. This group included acids, bases and neutral drugs.

Albumins↗
PubMed1988

Co-administered oral metoclopramide does not enhance the rate of absorption of oral diazepam.

Intravenous metoclopramide is known to increase the rate of absorption of oral diazepam if administered at the same time. It has been suggested that oral metoclopramide has the same effect. In this study, six healthy volunteers received oral diazepam (0.2 mg/kg) on two separate occasions, either alone or with oral metoclopramide (10 mg), given simultaneously. In contrast to the effects of intravenous metoclopramide, oral metoclopramide did not increase the rate of absorption of oral diazepam.

Absorption↗
PubMed1988

Drugs in human milk. Clinical pharmacokinetic considerations.

Drugs ingested by a lactating mother would be expected to appear in human milk to some extent and be ingested by a breast-feeding infant. Drugs pass from maternal plasma into milk by passive diffusion and are distributed within the aqueous, protein and lipid phases of milk. Distribution into milk will be affected by physiochemical characteristics of the drug: acid-base characteristics, relative protein binding in plasma and milk, and lipid solubility, as well as milk composition. The milk-to-plasma concentration ratio is the most commonly quoted index of drug distribution into human milk. However, calculation of the daily infant dose of drug ingested in milk, and from this the dose in milk relative to the maternal dose on a weight-adjusted basis, is a more relevant indicator of infant exposure to a drug. This is particularly true for drugs with a high volume of distribution, for which only a small proportion of the mother's dose is contained within the plasma and available for distribution into milk. A better indication of infant exposure to a drug is the steady-state plasma drug concentration in a breast-feeding infant, the major determinants of which are the dose rate (via milk) and the oral availability and clearance in the infant. Although in neonates the rate of absorption may be different from adults, there is little evidence that its extent is significantly different. Clearance, however, is impaired in very young infants, particularly if premature. The decreased clearance would result in a proportional increase in steady-state plasma concentrations in the breast-feeding infant. Consideration of the dose ingested in milk and the approximate clearance in infants of different ages allows estimation of likely steady-state plasma concentrations in breast-feeding infants. From these considerations, recommendations regarding the safety of drugs during breast-feeding can be made. Drugs which are very toxic or have dose-independent toxicity should be considered separately. Recommendations regarding 'social' drugs such as nicotine, alcohol, caffeine and theobromine are particularly difficult, as doses are uncontrolled and vary variable.

Breast Feeding↗