The application of drops containing ocular medicines to the conjunctival sac is the most common method of drug delivery to the anterior segment of the eye. Although this route of application seemingly displays numerous advantages, obtaining effective drug concentration at its site of action is challenging. The bioavailability of a topically applied drug depends on various factors related to the eye, to the drug and formulation, to the drop, and to the patient. The present article discusses their relative significance. From a drop applied to an eye, at most 5% of a drug dose enters the ocular structures. Of utmost importance for effective ocular drug delivery are patient compliance and the physicochemical properties of the drug. For a given concentration of an active substance, drop size may determine drug adverse effects but does not influence its efficacy.

A technique has been developed to record 18O2 dilution curves of an organ in vivo by use of 51Cr-labeled erythrocytes as a reference tracer. The technique employs anaerobic sampling of venous outflow following an intraarterial injection of tracer-laden blood and off-line determination of [18O2] and [51Cr] profiles in the venous outflow. O2 and reference indicator-dilution curves of cerebral circulation were recorded in eight experiments with six halothane-anesthetized dogs. Autologous blood labeled with the tracers was injected into a carotid artery, and brain venous outflow was sampled from the sagittal sinus. The total net extraction of O2 tracer was equal to the extraction of elemental O2. Instantaneous extraction of 18O2 along the outflow curve fell linearly with time, from an initial value of 0.6-0.7 to very small or even negative values toward the end of a pulse. This indicates that O2 undergoes a flow-limited distribution. In all experiments, the mean transit time of unmetabolized 18O2 was longer than the mean transit time of the Cr tracer. An index of the tissue O2 dilution space, hence the mean tissue PO2, is calculated from this data with the use of a modified central volume principle. This estimate of mean tissue PO2 increases as a linear function of sagittal sinus PO2 with a slope of 0.97. The method may provide an index of the critical PO2 of venous blood, the PO2 below which O2 diffusion from blood to tissue may limit its rate of metabolic uptake.

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Oxygen tension was measured in samples of blood and cisternal cerebrospinal fluid taken from anesthetized, paralyzed, and mechanically ventilated rabbits at various levels of arterial PO2. Cerebrospinal fluid oxygen tension (CSF PO2) was correlated with arterial PO2 (linear regression equation PCSFO2 = 0.2472 Pao2 + 42.34). During hypoxia CSF PO2 was higher than arterial PO2 in most experiments. These data can be attributed to the Bohr effect, which would increase the PO2 of the blood in choroid plexus capillaries as a result of its acidification. The acidification was suggested by Maren (Am. J. Physiol. 222: 885-889, 1972) to be a part of the ionic exchanges involved in cerebrospinal fluid formation. Such a mechanism may be of importance for supporting choroid plexus metabolism and function during hypoxia. This mechanism is most clearly seen in the rabbit.